Becky McCall

Tirzepatide (Zepbound for weight loss; Mounjaro for type 2 diabetes; Eli Lilly) consistently reduced body weight regardless of pretreatment body mass index (BMI) and reduced body weight and waist circumference regardless of duration of overweight or obesity.

The analyses — firstly of the impact of baseline BMI and secondly investigating the impact of the duration of overweight/obesity — are drawn from combined findings from the SURMOUNT 1-4 studies that examined the efficacy and safety of tirzepatide vs placebo. They are scheduled to be presented at May’s European Congress on Obesity (ECO) by Carel Le Roux, MD, University College Dublin, Ireland, and Giovanna Dr. Muscogiuri, MD, endocrinologist from the University of Naples Federico II, Naples, Italy, respectively.

The first analysis of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist, aimed to analyze the impact of baseline BMI category on weight reduction across the series of phase 3 trials.

More participants on tirzepatide than on placebo achieved the body weight reduction targets of 5%, 10%, and 15%. “Across the SURMOUNT 1-4 trials, treatment with tirzepatide, along with a reduced-calorie diet and increased physical activity, consistently resulted in clinically significant weight reductions of 5% or more, 10% or more, or 15% or more, as compared to placebo, regardless of baseline BMI subgroup, in adults with obesity or overweight (BMI of 27 and above),” said obesity specialist, Louis J. Aronne, MD, from the Comprehensive Weight Control Center, Weill Cornell Medicine, New York City, and coauthor of the BMI-related analysis.

Dr. Muscogiuri, who is first author of the second analysis that looked at the impact of duration of adiposity, and her coauthors concluded that, “Tirzepatide consistently reduced body weight and waist circumference in people living with obesity or overweight with weight-related comorbidities regardless of the duration of disease. These results are consistent with the overall findings from each study in the SURMOUNT program.”
 

Weight Loss Consistent Regardless of BMI

The SURMOUNT series of trials involved people with a BMI of 30 kg/m² and above, or 27 kg/m² with at least one weight-related comorbidity without type 2 diabetes (SURMOUNT-1, 72 weeks), with type 2 diabetes (SURMOUNT-2, 72 weeks), and without type 2 diabetes after a 12-week intensive lifestyle intervention (SURMOUNT-3, 72 weeks from randomization) or after an 88 week intervention (SURMOUNT-4, 36-week open label tirzepatide lead-in and 52 weeks following randomization).

BMI subgroups were defined by 27-30 (overweight), 30-35 (obesity class I), 35-40 (obesity class II), and 40 kg/m² and above (obesity class III). Percentage change in body weight from randomization to week 72 (SURMOUNT-1, -2, and -3) or to week 52 (SURMOUNT-4) was determined, as well as the proportions of participants achieving the weight reduction targets of 5%, 10%, and 15%. The per protocol analyses included all participants who received at least one dose of tirzepatide or placebo.

Across these BMI levels, up to 100% of tirzepatide-treated participants achieved weight reduction of 5% or more compared with 30% on placebo in SURMOUNT-1, up to 93% vs 43% in SURMOUNT-2, and up to 97% vs 15%, respectively, in SURMOUNT-3.

At least 10% weight reduction was achieved by up to 93% vs 16%, respectively, in SURMOUNT-1, up to 76% vs 14% in SURMOUNT-2, and up to 92% vs 8% in SURMOUNT-3.

Weight reduction of 15% was achieved by up to 85% compared with 7% of patients on tirzepatide and placebo, respectively, in SURMOUNT-1; up to 60% vs 3%, respectively, in SURMOUNT-2; and up to 78% vs 4% in SURMOUNT-3.

In SURMOUNT-4, during the 36-week open-label tirzepatide treatment, the mean body weight % or more reduction was 21%. Following this lead-in period, further weight reductions of 5% or more, 10%, and 15% or more were achieved by up to 70%, 39%, and 22%, respectively, of participants treated with tirzepatide compared with 2%, 2%, and 0% of patients on placebo.
 

Body Weight and Waist Circumference Reduced Regardless of Disease Duration

In this second presentation, participants were categorized based on duration with overweight/obesity at baseline (10 years or less, between 10 and 20 years, and above 20 years). Percentage body weight change; the proportions achieving weight loss targets of 5%, 10%, 15%, 20%, and 25%; and the change in waist circumference were analyzed.

Greater weight reductions were found in participants who took tirzepatide than in those who took placebo across the SURMOUNT 1-4 study endpoints, including weight reduction targets of 5%, 10%, 15%, 20%, and 25% compared with placebo-treated participants, regardless of disease duration, reported the authors in an early press release from ECO. The magnitude of weight reductions was generally similar across the disease duration categories.

For example, in the SURMOUNT-1 trial, for patients given 10-mg dose of tirzepatide, those with disease duration under 10 years lost 21% of their weight after 72 weeks compared with 20% body weight loss for those with 10-20 years disease duration and 23% for those with over 20 years disease duration.

In the SURMOUNT-2 trial (where all participants were also living with type 2 diabetes), for patients given the 10-mg dose of tirzepatide, those with disease duration under 10 years lost 12.6% of their body weight, while those with disease duration of 10-20 years lost 12.5%; in people living with overweight or obesity for over 20 years, 14.4% of body weight was lost.

Waist circumference also reduced to a greater extent than placebo for each disease duration category across the four studies, and again, these reductions were consistent across disease duration subgroups.

A difference between patients with and without type 2 diabetes was evident and requires further analysis to explore and understand why patients with type 2 diabetes have less weight loss in these trials than those without type 2 diabetes.

Asked to comment on the findings, Jens Juul Holst, MD, from the Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark, said that the results were as expected.

“The first abstract is said to show that there is the same effect regardless of the baseline BMI, but this is the expected outcome — nothing exciting there,” he told this news organization. “The second deals with the effects in people with different duration of adiposity. Again, it was equally effective in all groups and that was also the expected outcome, although important.”

“One question is whether one should treat people with BMI < 30 at all, and that depends on preexisting comorbidities — in particular metabolic syndrome, where treatment could be lifesaving and prevent complications,” added Dr. Holst.

This news organization also asked Jason Halford, ECO president, for his view on the findings. He remarked that with these weight loss drugs overall, “Usually weight loss tends to be proportional and actually greater in the lower BMI categories. This is partly because dosing is not done by body weight, and everyone gets the same doses irrespective of how they weigh. There is an argument that doses should be adjusted. The data suggests these drugs are so potent this does not occur for some reason.”

Dr. Holst added that, “In principle, for a given reduction in food intake, one would expect a similar reduction in body mass, and these agents should be dosed according to the size of the individual — since energy expenditure depends linearly on body weight, this is probably a reasonable measure. But what actually happens is dosing is according to the occurrence of side effects, which is a good pragmatic principle.”

Dr. Holst pointed out that the interesting question here is whether the very obese would somehow be resistant to the GLP-1 RAs (like leptin) — “they are not,” he noted.

He added that to his knowledge, the question around the role played by duration of the adiposity had not been explicitly looked at before. “However, the many individuals with obesity studied after GLP-1 RA treatment have varied widely with respect to duration and weight loss has not previously been known to depend on this, but there is no known physiological mechanism underpinning this.”

Tirzepatide (Mounjaro) was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of type 2 diabetes in 2022. In November 2023, the FDA approved tirzepatide (Zepbound) for chronic weight management in adults with BMI ≥ 30 kg/m² or BMI ≥ 27 kg/m² with at least one weight-related comorbidity. Also in November 2023, the EMA Committee for Medicinal Products for Human Use offered a positive opinion on extension of the Mounjaro label to include weight management in adults with BMI ≥ 30 kg/m² or BMI ≥ 27 kg/m² and at least one weight-related comorbid condition.

Dr. Holst had no conflicting interest with Eli Lilly but is a member of advisory boards for Novo Nordisk. This work (abstract 014) was funded by Eli Lilly and Company. Dr. Le Roux reported grants from the Irish Research Council, Science Foundation Ireland, Anabio, and the Health Research Board. He served on advisory boards and speaker panels of Novo Nordisk, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Glia, Irish Life Health, Boehringer Ingelheim, Currax, Zealand Pharma, and Rhythm Pharma. Dr. Le Roux is a member of the Irish Society for Nutrition and Metabolism outside the area of work commented on here. He was the chief medical officer and director of the Medical Device Division of Keyron in 2021. Both of these are unremunerated positions. Dr. Le Roux was a previous investor in Keyron, which develops endoscopically implantable medical devices intended to mimic the surgical procedures of sleeve gastrectomy and gastric bypass. No patients have been included in any of Keyron’s studies, and they are not listed on the stock market. Dr. Le Roux was gifted stock holdings in September 2021 and divested all stock holdings in Keyron in September 2021. He continues to provide scientific advice to Keyron for no remuneration. Dr. Le Roux provides obesity clinical care in the Beyond BMI clinic and is a shareholder in the clinic. Dr. Aronne reported receiving grants or personal fees from Altimmune, AstraZeneca, Boehringer Ingelheim, Eli Lilly, ERX, Gelesis, Intellihealth, Jamieson Wellness, Janssen, Novo Nordisk, Optum, Pfizer, Senda Biosciences, and Versanis and being a shareholder of Allurion, ERX Pharmaceuticals, Gelesis, Intellihealth, and Jamieson Wellness. FJ, TF, MM, LG, and LN are employees and shareholders of Eli Lilly and Company.

A version of this article appeared on Medscape.com.

Tirzepatide (Zepbound for weight loss; Mounjaro for type 2 diabetes; Eli Lilly) consistently reduced body weight regardless of pretreatment body mass index (BMI) and reduced body weight and waist circumference regardless of duration of overweight or obesity.

The analyses — firstly of the impact of baseline BMI and secondly investigating the impact of the duration of overweight/obesity — are drawn from combined findings from the SURMOUNT 1-4 studies that examined the efficacy and safety of tirzepatide vs placebo. They are scheduled to be presented at May’s European Congress on Obesity (ECO) by Carel Le Roux, MD, University College Dublin, Ireland, and Giovanna Dr. Muscogiuri, MD, endocrinologist from the University of Naples Federico II, Naples, Italy, respectively.

The first analysis of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist, aimed to analyze the impact of baseline BMI category on weight reduction across the series of phase 3 trials.

More participants on tirzepatide than on placebo achieved the body weight reduction targets of 5%, 10%, and 15%. “Across the SURMOUNT 1-4 trials, treatment with tirzepatide, along with a reduced-calorie diet and increased physical activity, consistently resulted in clinically significant weight reductions of 5% or more, 10% or more, or 15% or more, as compared to placebo, regardless of baseline BMI subgroup, in adults with obesity or overweight (BMI of 27 and above),” said obesity specialist, Louis J. Aronne, MD, from the Comprehensive Weight Control Center, Weill Cornell Medicine, New York City, and coauthor of the BMI-related analysis.

Dr. Muscogiuri, who is first author of the second analysis that looked at the impact of duration of adiposity, and her coauthors concluded that, “Tirzepatide consistently reduced body weight and waist circumference in people living with obesity or overweight with weight-related comorbidities regardless of the duration of disease. These results are consistent with the overall findings from each study in the SURMOUNT program.”
 

Weight Loss Consistent Regardless of BMI

The SURMOUNT series of trials involved people with a BMI of 30 kg/m² and above, or 27 kg/m² with at least one weight-related comorbidity without type 2 diabetes (SURMOUNT-1, 72 weeks), with type 2 diabetes (SURMOUNT-2, 72 weeks), and without type 2 diabetes after a 12-week intensive lifestyle intervention (SURMOUNT-3, 72 weeks from randomization) or after an 88 week intervention (SURMOUNT-4, 36-week open label tirzepatide lead-in and 52 weeks following randomization).

BMI subgroups were defined by 27-30 (overweight), 30-35 (obesity class I), 35-40 (obesity class II), and 40 kg/m² and above (obesity class III). Percentage change in body weight from randomization to week 72 (SURMOUNT-1, -2, and -3) or to week 52 (SURMOUNT-4) was determined, as well as the proportions of participants achieving the weight reduction targets of 5%, 10%, and 15%. The per protocol analyses included all participants who received at least one dose of tirzepatide or placebo.

Across these BMI levels, up to 100% of tirzepatide-treated participants achieved weight reduction of 5% or more compared with 30% on placebo in SURMOUNT-1, up to 93% vs 43% in SURMOUNT-2, and up to 97% vs 15%, respectively, in SURMOUNT-3.

At least 10% weight reduction was achieved by up to 93% vs 16%, respectively, in SURMOUNT-1, up to 76% vs 14% in SURMOUNT-2, and up to 92% vs 8% in SURMOUNT-3.

Weight reduction of 15% was achieved by up to 85% compared with 7% of patients on tirzepatide and placebo, respectively, in SURMOUNT-1; up to 60% vs 3%, respectively, in SURMOUNT-2; and up to 78% vs 4% in SURMOUNT-3.

In SURMOUNT-4, during the 36-week open-label tirzepatide treatment, the mean body weight % or more reduction was 21%. Following this lead-in period, further weight reductions of 5% or more, 10%, and 15% or more were achieved by up to 70%, 39%, and 22%, respectively, of participants treated with tirzepatide compared with 2%, 2%, and 0% of patients on placebo.
 

Body Weight and Waist Circumference Reduced Regardless of Disease Duration

In this second presentation, participants were categorized based on duration with overweight/obesity at baseline (10 years or less, between 10 and 20 years, and above 20 years). Percentage body weight change; the proportions achieving weight loss targets of 5%, 10%, 15%, 20%, and 25%; and the change in waist circumference were analyzed.

Greater weight reductions were found in participants who took tirzepatide than in those who took placebo across the SURMOUNT 1-4 study endpoints, including weight reduction targets of 5%, 10%, 15%, 20%, and 25% compared with placebo-treated participants, regardless of disease duration, reported the authors in an early press release from ECO. The magnitude of weight reductions was generally similar across the disease duration categories.

For example, in the SURMOUNT-1 trial, for patients given 10-mg dose of tirzepatide, those with disease duration under 10 years lost 21% of their weight after 72 weeks compared with 20% body weight loss for those with 10-20 years disease duration and 23% for those with over 20 years disease duration.

In the SURMOUNT-2 trial (where all participants were also living with type 2 diabetes), for patients given the 10-mg dose of tirzepatide, those with disease duration under 10 years lost 12.6% of their body weight, while those with disease duration of 10-20 years lost 12.5%; in people living with overweight or obesity for over 20 years, 14.4% of body weight was lost.

Waist circumference also reduced to a greater extent than placebo for each disease duration category across the four studies, and again, these reductions were consistent across disease duration subgroups.

A difference between patients with and without type 2 diabetes was evident and requires further analysis to explore and understand why patients with type 2 diabetes have less weight loss in these trials than those without type 2 diabetes.

Asked to comment on the findings, Jens Juul Holst, MD, from the Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark, said that the results were as expected.

“The first abstract is said to show that there is the same effect regardless of the baseline BMI, but this is the expected outcome — nothing exciting there,” he told this news organization. “The second deals with the effects in people with different duration of adiposity. Again, it was equally effective in all groups and that was also the expected outcome, although important.”

“One question is whether one should treat people with BMI < 30 at all, and that depends on preexisting comorbidities — in particular metabolic syndrome, where treatment could be lifesaving and prevent complications,” added Dr. Holst.

This news organization also asked Jason Halford, ECO president, for his view on the findings. He remarked that with these weight loss drugs overall, “Usually weight loss tends to be proportional and actually greater in the lower BMI categories. This is partly because dosing is not done by body weight, and everyone gets the same doses irrespective of how they weigh. There is an argument that doses should be adjusted. The data suggests these drugs are so potent this does not occur for some reason.”

Dr. Holst added that, “In principle, for a given reduction in food intake, one would expect a similar reduction in body mass, and these agents should be dosed according to the size of the individual — since energy expenditure depends linearly on body weight, this is probably a reasonable measure. But what actually happens is dosing is according to the occurrence of side effects, which is a good pragmatic principle.”

Dr. Holst pointed out that the interesting question here is whether the very obese would somehow be resistant to the GLP-1 RAs (like leptin) — “they are not,” he noted.

He added that to his knowledge, the question around the role played by duration of the adiposity had not been explicitly looked at before. “However, the many individuals with obesity studied after GLP-1 RA treatment have varied widely with respect to duration and weight loss has not previously been known to depend on this, but there is no known physiological mechanism underpinning this.”

Tirzepatide (Mounjaro) was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of type 2 diabetes in 2022. In November 2023, the FDA approved tirzepatide (Zepbound) for chronic weight management in adults with BMI ≥ 30 kg/m² or BMI ≥ 27 kg/m² with at least one weight-related comorbidity. Also in November 2023, the EMA Committee for Medicinal Products for Human Use offered a positive opinion on extension of the Mounjaro label to include weight management in adults with BMI ≥ 30 kg/m² or BMI ≥ 27 kg/m² and at least one weight-related comorbid condition.

Dr. Holst had no conflicting interest with Eli Lilly but is a member of advisory boards for Novo Nordisk. This work (abstract 014) was funded by Eli Lilly and Company. Dr. Le Roux reported grants from the Irish Research Council, Science Foundation Ireland, Anabio, and the Health Research Board. He served on advisory boards and speaker panels of Novo Nordisk, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Glia, Irish Life Health, Boehringer Ingelheim, Currax, Zealand Pharma, and Rhythm Pharma. Dr. Le Roux is a member of the Irish Society for Nutrition and Metabolism outside the area of work commented on here. He was the chief medical officer and director of the Medical Device Division of Keyron in 2021. Both of these are unremunerated positions. Dr. Le Roux was a previous investor in Keyron, which develops endoscopically implantable medical devices intended to mimic the surgical procedures of sleeve gastrectomy and gastric bypass. No patients have been included in any of Keyron’s studies, and they are not listed on the stock market. Dr. Le Roux was gifted stock holdings in September 2021 and divested all stock holdings in Keyron in September 2021. He continues to provide scientific advice to Keyron for no remuneration. Dr. Le Roux provides obesity clinical care in the Beyond BMI clinic and is a shareholder in the clinic. Dr. Aronne reported receiving grants or personal fees from Altimmune, AstraZeneca, Boehringer Ingelheim, Eli Lilly, ERX, Gelesis, Intellihealth, Jamieson Wellness, Janssen, Novo Nordisk, Optum, Pfizer, Senda Biosciences, and Versanis and being a shareholder of Allurion, ERX Pharmaceuticals, Gelesis, Intellihealth, and Jamieson Wellness. FJ, TF, MM, LG, and LN are employees and shareholders of Eli Lilly and Company.

A version of this article appeared on Medscape.com.

Tirzepatide (Zepbound for weight loss; Mounjaro for type 2 diabetes; Eli Lilly) consistently reduced body weight regardless of pretreatment body mass index (BMI) and reduced body weight and waist circumference regardless of duration of overweight or obesity.

The analyses — firstly of the impact of baseline BMI and secondly investigating the impact of the duration of overweight/obesity — are drawn from combined findings from the SURMOUNT 1-4 studies that examined the efficacy and safety of tirzepatide vs placebo. They are scheduled to be presented at May’s European Congress on Obesity (ECO) by Carel Le Roux, MD, University College Dublin, Ireland, and Giovanna Dr. Muscogiuri, MD, endocrinologist from the University of Naples Federico II, Naples, Italy, respectively.

The first analysis of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist, aimed to analyze the impact of baseline BMI category on weight reduction across the series of phase 3 trials.

More participants on tirzepatide than on placebo achieved the body weight reduction targets of 5%, 10%, and 15%. “Across the SURMOUNT 1-4 trials, treatment with tirzepatide, along with a reduced-calorie diet and increased physical activity, consistently resulted in clinically significant weight reductions of 5% or more, 10% or more, or 15% or more, as compared to placebo, regardless of baseline BMI subgroup, in adults with obesity or overweight (BMI of 27 and above),” said obesity specialist, Louis J. Aronne, MD, from the Comprehensive Weight Control Center, Weill Cornell Medicine, New York City, and coauthor of the BMI-related analysis.

Dr. Muscogiuri, who is first author of the second analysis that looked at the impact of duration of adiposity, and her coauthors concluded that, “Tirzepatide consistently reduced body weight and waist circumference in people living with obesity or overweight with weight-related comorbidities regardless of the duration of disease. These results are consistent with the overall findings from each study in the SURMOUNT program.”
 

Weight Loss Consistent Regardless of BMI

The SURMOUNT series of trials involved people with a BMI of 30 kg/m² and above, or 27 kg/m² with at least one weight-related comorbidity without type 2 diabetes (SURMOUNT-1, 72 weeks), with type 2 diabetes (SURMOUNT-2, 72 weeks), and without type 2 diabetes after a 12-week intensive lifestyle intervention (SURMOUNT-3, 72 weeks from randomization) or after an 88 week intervention (SURMOUNT-4, 36-week open label tirzepatide lead-in and 52 weeks following randomization).

BMI subgroups were defined by 27-30 (overweight), 30-35 (obesity class I), 35-40 (obesity class II), and 40 kg/m² and above (obesity class III). Percentage change in body weight from randomization to week 72 (SURMOUNT-1, -2, and -3) or to week 52 (SURMOUNT-4) was determined, as well as the proportions of participants achieving the weight reduction targets of 5%, 10%, and 15%. The per protocol analyses included all participants who received at least one dose of tirzepatide or placebo.

Across these BMI levels, up to 100% of tirzepatide-treated participants achieved weight reduction of 5% or more compared with 30% on placebo in SURMOUNT-1, up to 93% vs 43% in SURMOUNT-2, and up to 97% vs 15%, respectively, in SURMOUNT-3.

At least 10% weight reduction was achieved by up to 93% vs 16%, respectively, in SURMOUNT-1, up to 76% vs 14% in SURMOUNT-2, and up to 92% vs 8% in SURMOUNT-3.

Weight reduction of 15% was achieved by up to 85% compared with 7% of patients on tirzepatide and placebo, respectively, in SURMOUNT-1; up to 60% vs 3%, respectively, in SURMOUNT-2; and up to 78% vs 4% in SURMOUNT-3.

In SURMOUNT-4, during the 36-week open-label tirzepatide treatment, the mean body weight % or more reduction was 21%. Following this lead-in period, further weight reductions of 5% or more, 10%, and 15% or more were achieved by up to 70%, 39%, and 22%, respectively, of participants treated with tirzepatide compared with 2%, 2%, and 0% of patients on placebo.
 

Body Weight and Waist Circumference Reduced Regardless of Disease Duration

In this second presentation, participants were categorized based on duration with overweight/obesity at baseline (10 years or less, between 10 and 20 years, and above 20 years). Percentage body weight change; the proportions achieving weight loss targets of 5%, 10%, 15%, 20%, and 25%; and the change in waist circumference were analyzed.

Greater weight reductions were found in participants who took tirzepatide than in those who took placebo across the SURMOUNT 1-4 study endpoints, including weight reduction targets of 5%, 10%, 15%, 20%, and 25% compared with placebo-treated participants, regardless of disease duration, reported the authors in an early press release from ECO. The magnitude of weight reductions was generally similar across the disease duration categories.

For example, in the SURMOUNT-1 trial, for patients given 10-mg dose of tirzepatide, those with disease duration under 10 years lost 21% of their weight after 72 weeks compared with 20% body weight loss for those with 10-20 years disease duration and 23% for those with over 20 years disease duration.

In the SURMOUNT-2 trial (where all participants were also living with type 2 diabetes), for patients given the 10-mg dose of tirzepatide, those with disease duration under 10 years lost 12.6% of their body weight, while those with disease duration of 10-20 years lost 12.5%; in people living with overweight or obesity for over 20 years, 14.4% of body weight was lost.

Waist circumference also reduced to a greater extent than placebo for each disease duration category across the four studies, and again, these reductions were consistent across disease duration subgroups.

A difference between patients with and without type 2 diabetes was evident and requires further analysis to explore and understand why patients with type 2 diabetes have less weight loss in these trials than those without type 2 diabetes.

Asked to comment on the findings, Jens Juul Holst, MD, from the Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark, said that the results were as expected.

“The first abstract is said to show that there is the same effect regardless of the baseline BMI, but this is the expected outcome — nothing exciting there,” he told this news organization. “The second deals with the effects in people with different duration of adiposity. Again, it was equally effective in all groups and that was also the expected outcome, although important.”

“One question is whether one should treat people with BMI < 30 at all, and that depends on preexisting comorbidities — in particular metabolic syndrome, where treatment could be lifesaving and prevent complications,” added Dr. Holst.

This news organization also asked Jason Halford, ECO president, for his view on the findings. He remarked that with these weight loss drugs overall, “Usually weight loss tends to be proportional and actually greater in the lower BMI categories. This is partly because dosing is not done by body weight, and everyone gets the same doses irrespective of how they weigh. There is an argument that doses should be adjusted. The data suggests these drugs are so potent this does not occur for some reason.”

Dr. Holst added that, “In principle, for a given reduction in food intake, one would expect a similar reduction in body mass, and these agents should be dosed according to the size of the individual — since energy expenditure depends linearly on body weight, this is probably a reasonable measure. But what actually happens is dosing is according to the occurrence of side effects, which is a good pragmatic principle.”

Dr. Holst pointed out that the interesting question here is whether the very obese would somehow be resistant to the GLP-1 RAs (like leptin) — “they are not,” he noted.

He added that to his knowledge, the question around the role played by duration of the adiposity had not been explicitly looked at before. “However, the many individuals with obesity studied after GLP-1 RA treatment have varied widely with respect to duration and weight loss has not previously been known to depend on this, but there is no known physiological mechanism underpinning this.”

Tirzepatide (Mounjaro) was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of type 2 diabetes in 2022. In November 2023, the FDA approved tirzepatide (Zepbound) for chronic weight management in adults with BMI ≥ 30 kg/m² or BMI ≥ 27 kg/m² with at least one weight-related comorbidity. Also in November 2023, the EMA Committee for Medicinal Products for Human Use offered a positive opinion on extension of the Mounjaro label to include weight management in adults with BMI ≥ 30 kg/m² or BMI ≥ 27 kg/m² and at least one weight-related comorbid condition.

Dr. Holst had no conflicting interest with Eli Lilly but is a member of advisory boards for Novo Nordisk. This work (abstract 014) was funded by Eli Lilly and Company. Dr. Le Roux reported grants from the Irish Research Council, Science Foundation Ireland, Anabio, and the Health Research Board. He served on advisory boards and speaker panels of Novo Nordisk, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Glia, Irish Life Health, Boehringer Ingelheim, Currax, Zealand Pharma, and Rhythm Pharma. Dr. Le Roux is a member of the Irish Society for Nutrition and Metabolism outside the area of work commented on here. He was the chief medical officer and director of the Medical Device Division of Keyron in 2021. Both of these are unremunerated positions. Dr. Le Roux was a previous investor in Keyron, which develops endoscopically implantable medical devices intended to mimic the surgical procedures of sleeve gastrectomy and gastric bypass. No patients have been included in any of Keyron’s studies, and they are not listed on the stock market. Dr. Le Roux was gifted stock holdings in September 2021 and divested all stock holdings in Keyron in September 2021. He continues to provide scientific advice to Keyron for no remuneration. Dr. Le Roux provides obesity clinical care in the Beyond BMI clinic and is a shareholder in the clinic. Dr. Aronne reported receiving grants or personal fees from Altimmune, AstraZeneca, Boehringer Ingelheim, Eli Lilly, ERX, Gelesis, Intellihealth, Jamieson Wellness, Janssen, Novo Nordisk, Optum, Pfizer, Senda Biosciences, and Versanis and being a shareholder of Allurion, ERX Pharmaceuticals, Gelesis, Intellihealth, and Jamieson Wellness. FJ, TF, MM, LG, and LN are employees and shareholders of Eli Lilly and Company.

A version of this article appeared on Medscape.com.

STOCKHOLM — An artificial intelligence (AI)–assisted image-enhanced endoscopy system accurately assessed vascular healing and predicted long-term clinical relapse in patients with ulcerative colitis (UC), according to data from the study of a novel investigational tool. 

Clinical relapse was predicted in 3% of patients identified as having vascular healing in all segments compared with 23.9% in those with vascular activity (ie, one or more segments were active), reported Yasuharu Maeda, MD, gastroenterologist from Showa University Northern Yokohama Hospital, Digestive Disease Center, Yokohama, Japan.

In patients with a Mayo Endoscopic Score (MES) ≤ 1, the clinical relapse rate was 3% and 18.6% in the vascular healing and vascular active groups, respectively, he said. 

Endoscopic remission is a crucial treat-to-target goal in patients with UC, and image-enhanced endoscopy is spreading in routine practice as a way to detect inflammation and to predict outcomes, Dr. Maeda said. 

“Image-enhanced vascular findings lead to a stronger correlation with histological activities and long-term prognosis compared with white light endoscopy assessment,” he explained. “It also means that assessment can be done on-site without biopsy, pathologist effort, and associated costs; however, specialist training is required to achieve a high accuracy in outputs.” 

Dr. Maeda presented the data (Abstract OP16) at the annual congress of the European Crohn’s and Colitis Organisation.

Stratifying the Relapse Risk

Dr. Maeda and colleagues developed a novel AI-based narrow-band imaging system, training it by using 8853 images from 167 patients with UC. 

The AI system, EndoBRAIN-UC (Cybernet System Corp, Tokyo), is in use and currently adapted for only one endoscope, the Endocyto CFH290EC (Olympus EMEA, Tokyo), but for the purpose of this study, it was trained on images from five different scopes. 

“By combining narrow-band imaging and AI, we developed a system where we can differentiate between vascular activity and vascular healing. This allows us to predict relapse,” Dr. Maeda said.

In an open-label, prospective cohort study, they tested the system with the aim of assessing the efficacy of AI-identified vascular healing to stratify the relapse risk in 100 patients showing clinical remission of UC (ie, partial MES ≤ 1). 

Patient characteristics were similar between both groups with an average disease duration of 10 years. 

In the vascular healing group (n = 33), the average age was 52 years, 20% were men, 58% had extensive colitis, and 52% had a MES score of 0.

In the vascular active group (n = 67), the average age was 56 years, 32% were men, 61% had extensive colitis, and 25% had a MES score of 0.

Colonoscopy was performed using the AI system to identify mucosa as healing or active for six colorectal segments of each patient. The MES and histologic assessment for these segments were also recorded. Patients were then followed for up to 12 months and assessed for clinical relapse.

The clinical relapse rate was higher in the vascular active group than in the vascular healing group as identified by AI. 

“We only evaluated the diagnostic output of the AI but obtained white light endoscopies and biopsies for contrast studies,” Dr. Maeda noted.

They also looked at whether the endoscopist’s level of experience (ie, trainee or expert) was important but found that clinical relapse predictive values were independent of the endoscopist’s experience. 

Still in the Early Stages

AI-assisted colonoscopy work is still at an early stage , said session co-moderator, Monika Ferlitsch, MD, head of Internal Medicine Department II, gastroenterology and hepatology, Evangelical Hospital, in Vienna, Austria. 

We now have initial results, but “I suspect it will take 10-20 years for implementation into routine clinical practice,” she said. 

The best outcome for our patients is to be able to predict response to therapy and recurrence rates, “and we see this is possible now with AI. But of course, we need more clinical data to support it,” Dr. Ferlitsch said.

Dr. Maeda and Dr. Ferlitsch have declared no financial disclosures.

A version of this article appeared on Medscape.com.

STOCKHOLM — An artificial intelligence (AI)–assisted image-enhanced endoscopy system accurately assessed vascular healing and predicted long-term clinical relapse in patients with ulcerative colitis (UC), according to data from the study of a novel investigational tool. 

Clinical relapse was predicted in 3% of patients identified as having vascular healing in all segments compared with 23.9% in those with vascular activity (ie, one or more segments were active), reported Yasuharu Maeda, MD, gastroenterologist from Showa University Northern Yokohama Hospital, Digestive Disease Center, Yokohama, Japan.

In patients with a Mayo Endoscopic Score (MES) ≤ 1, the clinical relapse rate was 3% and 18.6% in the vascular healing and vascular active groups, respectively, he said. 

Endoscopic remission is a crucial treat-to-target goal in patients with UC, and image-enhanced endoscopy is spreading in routine practice as a way to detect inflammation and to predict outcomes, Dr. Maeda said. 

“Image-enhanced vascular findings lead to a stronger correlation with histological activities and long-term prognosis compared with white light endoscopy assessment,” he explained. “It also means that assessment can be done on-site without biopsy, pathologist effort, and associated costs; however, specialist training is required to achieve a high accuracy in outputs.” 

Dr. Maeda presented the data (Abstract OP16) at the annual congress of the European Crohn’s and Colitis Organisation.

Stratifying the Relapse Risk

Dr. Maeda and colleagues developed a novel AI-based narrow-band imaging system, training it by using 8853 images from 167 patients with UC. 

The AI system, EndoBRAIN-UC (Cybernet System Corp, Tokyo), is in use and currently adapted for only one endoscope, the Endocyto CFH290EC (Olympus EMEA, Tokyo), but for the purpose of this study, it was trained on images from five different scopes. 

“By combining narrow-band imaging and AI, we developed a system where we can differentiate between vascular activity and vascular healing. This allows us to predict relapse,” Dr. Maeda said.

In an open-label, prospective cohort study, they tested the system with the aim of assessing the efficacy of AI-identified vascular healing to stratify the relapse risk in 100 patients showing clinical remission of UC (ie, partial MES ≤ 1). 

Patient characteristics were similar between both groups with an average disease duration of 10 years. 

In the vascular healing group (n = 33), the average age was 52 years, 20% were men, 58% had extensive colitis, and 52% had a MES score of 0.

In the vascular active group (n = 67), the average age was 56 years, 32% were men, 61% had extensive colitis, and 25% had a MES score of 0.

Colonoscopy was performed using the AI system to identify mucosa as healing or active for six colorectal segments of each patient. The MES and histologic assessment for these segments were also recorded. Patients were then followed for up to 12 months and assessed for clinical relapse.

The clinical relapse rate was higher in the vascular active group than in the vascular healing group as identified by AI. 

“We only evaluated the diagnostic output of the AI but obtained white light endoscopies and biopsies for contrast studies,” Dr. Maeda noted.

They also looked at whether the endoscopist’s level of experience (ie, trainee or expert) was important but found that clinical relapse predictive values were independent of the endoscopist’s experience. 

Still in the Early Stages

AI-assisted colonoscopy work is still at an early stage , said session co-moderator, Monika Ferlitsch, MD, head of Internal Medicine Department II, gastroenterology and hepatology, Evangelical Hospital, in Vienna, Austria. 

We now have initial results, but “I suspect it will take 10-20 years for implementation into routine clinical practice,” she said. 

The best outcome for our patients is to be able to predict response to therapy and recurrence rates, “and we see this is possible now with AI. But of course, we need more clinical data to support it,” Dr. Ferlitsch said.

Dr. Maeda and Dr. Ferlitsch have declared no financial disclosures.

A version of this article appeared on Medscape.com.

STOCKHOLM — An artificial intelligence (AI)–assisted image-enhanced endoscopy system accurately assessed vascular healing and predicted long-term clinical relapse in patients with ulcerative colitis (UC), according to data from the study of a novel investigational tool. 

Clinical relapse was predicted in 3% of patients identified as having vascular healing in all segments compared with 23.9% in those with vascular activity (ie, one or more segments were active), reported Yasuharu Maeda, MD, gastroenterologist from Showa University Northern Yokohama Hospital, Digestive Disease Center, Yokohama, Japan.

In patients with a Mayo Endoscopic Score (MES) ≤ 1, the clinical relapse rate was 3% and 18.6% in the vascular healing and vascular active groups, respectively, he said. 

Endoscopic remission is a crucial treat-to-target goal in patients with UC, and image-enhanced endoscopy is spreading in routine practice as a way to detect inflammation and to predict outcomes, Dr. Maeda said. 

“Image-enhanced vascular findings lead to a stronger correlation with histological activities and long-term prognosis compared with white light endoscopy assessment,” he explained. “It also means that assessment can be done on-site without biopsy, pathologist effort, and associated costs; however, specialist training is required to achieve a high accuracy in outputs.” 

Dr. Maeda presented the data (Abstract OP16) at the annual congress of the European Crohn’s and Colitis Organisation.

Stratifying the Relapse Risk

Dr. Maeda and colleagues developed a novel AI-based narrow-band imaging system, training it by using 8853 images from 167 patients with UC. 

The AI system, EndoBRAIN-UC (Cybernet System Corp, Tokyo), is in use and currently adapted for only one endoscope, the Endocyto CFH290EC (Olympus EMEA, Tokyo), but for the purpose of this study, it was trained on images from five different scopes. 

“By combining narrow-band imaging and AI, we developed a system where we can differentiate between vascular activity and vascular healing. This allows us to predict relapse,” Dr. Maeda said.

In an open-label, prospective cohort study, they tested the system with the aim of assessing the efficacy of AI-identified vascular healing to stratify the relapse risk in 100 patients showing clinical remission of UC (ie, partial MES ≤ 1). 

Patient characteristics were similar between both groups with an average disease duration of 10 years. 

In the vascular healing group (n = 33), the average age was 52 years, 20% were men, 58% had extensive colitis, and 52% had a MES score of 0.

In the vascular active group (n = 67), the average age was 56 years, 32% were men, 61% had extensive colitis, and 25% had a MES score of 0.

Colonoscopy was performed using the AI system to identify mucosa as healing or active for six colorectal segments of each patient. The MES and histologic assessment for these segments were also recorded. Patients were then followed for up to 12 months and assessed for clinical relapse.

The clinical relapse rate was higher in the vascular active group than in the vascular healing group as identified by AI. 

“We only evaluated the diagnostic output of the AI but obtained white light endoscopies and biopsies for contrast studies,” Dr. Maeda noted.

They also looked at whether the endoscopist’s level of experience (ie, trainee or expert) was important but found that clinical relapse predictive values were independent of the endoscopist’s experience. 

Still in the Early Stages

AI-assisted colonoscopy work is still at an early stage , said session co-moderator, Monika Ferlitsch, MD, head of Internal Medicine Department II, gastroenterology and hepatology, Evangelical Hospital, in Vienna, Austria. 

We now have initial results, but “I suspect it will take 10-20 years for implementation into routine clinical practice,” she said. 

The best outcome for our patients is to be able to predict response to therapy and recurrence rates, “and we see this is possible now with AI. But of course, we need more clinical data to support it,” Dr. Ferlitsch said.

Dr. Maeda and Dr. Ferlitsch have declared no financial disclosures.

A version of this article appeared on Medscape.com.

STOCKHOLM — Eight live bacterial strains have been identified as having the potential to regulate the inflammatory imbalance in the gut microbiome of patients with mild to moderate ulcerative colitis (UC). 

The eight-strain live biotherapeutic product (MB310, Microbiotica) is due to enter its first clinical trial later this year.

In patients with UC who showed clinical benefit after fecal microbiota transplantation (FMT), these eight specific bacterial strains were shown to be consistently elevated, reported Ron Carter, MD, chief medical officer at Microbiotica, Cambridge, UK, the company developing the product. 

In addition, “in lab studies, we’ve found they exhibit anti-inflammatory effects when incubated with different cells of the immune system,” he explained. With the biotherapeutic product, “we want to prompt the immune system to realign the gut inflammation” in UC.

On February 23, at the annual congress of the European Crohn’s and Colitis Organisation, Dr. Carter presented the work-to-date and the near-term plans for a phase 1b randomized, placebo-controlled, double-blind trial to be conducted across roughly 20 sites in Europe (Abstract DOP 67). The trial, COMPOSER-1, will investigate the engraftment and initial signs of clinical activity of MB310 in 30 patients with active, mild to moderate UC (modified Mayo score 4-7; endoscopic subscore ≥ 2).

 Calming Inflammation With Specific Bacteria 

To date, the researchers have focused on identifying bacterial species that correlate with clinical outcomes in individual patients with UC after treatment with FMT. Dr. Carter and colleagues worked in collaboration with Sam Costello, MBBS, gastroenterologist at The Queen Elizabeth Hospital in Adelaide, Australia.

The initial research involved analyzing stool samples from a round 70 patients diagnosed with mild to moderate UC, who were randomly assigned to receive either pooled, anaerobically prepared, healthy donor FMT, or their own autologous FMT as a comparative control. FMT was delivered via colonoscopy and two enemas over 7 days. The primary endpoint of the study was achieving steroid-free remission of UC on the basis of specific Mayo scores, at the end of week 8.

“Results indicated that the group receiving the pooled donor FMT showed a 32% success rate with respect to the primary outcome compared with only 9% of the control group,” said Dr. Carter. “This suggested a promising therapeutic strategy.”

Based on these outcomes, Microbiotica then decided to conduct a local study in which they analyzed fecal samples from FMT donors and from pre-FMT and post-FMT recipients in order to precisely identify which bacterial species were associated with clinical response. 

“With our precision microbiome analysis platform, we determined eight bacterial species that were consistently elevated in FMT responders, but absent or not elevated in non-responders,” reported Dr. Carter.

Next, they carried out subspecies-level bioinformatic analysis and identified one bacterial strain from each of the eight species, which were then cultured individually, freeze-dried, and combined into a custom delayed-release capsule. 

The researchers tested the resulting live biotherapeutic product in cellular assays using human cell lines to confirm that they effectively modulated immune functions. 

The cellular assays showed that in epithelial cell monolayer tests, MB310 not only enhanced barrier integrity but also protected the cellular barrier from inflammation. 

The eight bacterial strain combination also exhibited anti-inflammatory effects when incubated with different primary innate immune cells, dendritic cells, and M1 macrophages. 

And, Dr. Carter emphasized, the specific MB310 bacterial strains were found to regulate T-cells directly or via metabolites.

Moving in the Right Direction

Julien Kirchgesner, MD, Saint-Antoine Hospital and Sorbonne University, Paris, France, who co-moderated the session where the research was presented, welcomed the work.

“Many more trials need to be done before we see this enter the clinic, but this is moving in the right direction,” Dr. Kirchgesner noted.

“We need to find only the functionally active bacterial strains, rather than just take the fecal transplant alone [as is done with FMT],” he said. That is what is being done here.

“The researchers want to identify which bacterial strains will impact the effectiveness in patients, and to select for these strains before industrializing the process and producing them at the optimal strength, at scale,” Dr. Kirchgesner said.

Dr. Carter is chief medical officer at Microbiotica and Dr Kirshgensner has no financial disclosures.

A version of this article appeared on Medscape.com.

STOCKHOLM — Eight live bacterial strains have been identified as having the potential to regulate the inflammatory imbalance in the gut microbiome of patients with mild to moderate ulcerative colitis (UC). 

The eight-strain live biotherapeutic product (MB310, Microbiotica) is due to enter its first clinical trial later this year.

In patients with UC who showed clinical benefit after fecal microbiota transplantation (FMT), these eight specific bacterial strains were shown to be consistently elevated, reported Ron Carter, MD, chief medical officer at Microbiotica, Cambridge, UK, the company developing the product. 

In addition, “in lab studies, we’ve found they exhibit anti-inflammatory effects when incubated with different cells of the immune system,” he explained. With the biotherapeutic product, “we want to prompt the immune system to realign the gut inflammation” in UC.

On February 23, at the annual congress of the European Crohn’s and Colitis Organisation, Dr. Carter presented the work-to-date and the near-term plans for a phase 1b randomized, placebo-controlled, double-blind trial to be conducted across roughly 20 sites in Europe (Abstract DOP 67). The trial, COMPOSER-1, will investigate the engraftment and initial signs of clinical activity of MB310 in 30 patients with active, mild to moderate UC (modified Mayo score 4-7; endoscopic subscore ≥ 2).

 Calming Inflammation With Specific Bacteria 

To date, the researchers have focused on identifying bacterial species that correlate with clinical outcomes in individual patients with UC after treatment with FMT. Dr. Carter and colleagues worked in collaboration with Sam Costello, MBBS, gastroenterologist at The Queen Elizabeth Hospital in Adelaide, Australia.

The initial research involved analyzing stool samples from a round 70 patients diagnosed with mild to moderate UC, who were randomly assigned to receive either pooled, anaerobically prepared, healthy donor FMT, or their own autologous FMT as a comparative control. FMT was delivered via colonoscopy and two enemas over 7 days. The primary endpoint of the study was achieving steroid-free remission of UC on the basis of specific Mayo scores, at the end of week 8.

“Results indicated that the group receiving the pooled donor FMT showed a 32% success rate with respect to the primary outcome compared with only 9% of the control group,” said Dr. Carter. “This suggested a promising therapeutic strategy.”

Based on these outcomes, Microbiotica then decided to conduct a local study in which they analyzed fecal samples from FMT donors and from pre-FMT and post-FMT recipients in order to precisely identify which bacterial species were associated with clinical response. 

“With our precision microbiome analysis platform, we determined eight bacterial species that were consistently elevated in FMT responders, but absent or not elevated in non-responders,” reported Dr. Carter.

Next, they carried out subspecies-level bioinformatic analysis and identified one bacterial strain from each of the eight species, which were then cultured individually, freeze-dried, and combined into a custom delayed-release capsule. 

The researchers tested the resulting live biotherapeutic product in cellular assays using human cell lines to confirm that they effectively modulated immune functions. 

The cellular assays showed that in epithelial cell monolayer tests, MB310 not only enhanced barrier integrity but also protected the cellular barrier from inflammation. 

The eight bacterial strain combination also exhibited anti-inflammatory effects when incubated with different primary innate immune cells, dendritic cells, and M1 macrophages. 

And, Dr. Carter emphasized, the specific MB310 bacterial strains were found to regulate T-cells directly or via metabolites.

Moving in the Right Direction

Julien Kirchgesner, MD, Saint-Antoine Hospital and Sorbonne University, Paris, France, who co-moderated the session where the research was presented, welcomed the work.

“Many more trials need to be done before we see this enter the clinic, but this is moving in the right direction,” Dr. Kirchgesner noted.

“We need to find only the functionally active bacterial strains, rather than just take the fecal transplant alone [as is done with FMT],” he said. That is what is being done here.

“The researchers want to identify which bacterial strains will impact the effectiveness in patients, and to select for these strains before industrializing the process and producing them at the optimal strength, at scale,” Dr. Kirchgesner said.

Dr. Carter is chief medical officer at Microbiotica and Dr Kirshgensner has no financial disclosures.

A version of this article appeared on Medscape.com.

STOCKHOLM — Eight live bacterial strains have been identified as having the potential to regulate the inflammatory imbalance in the gut microbiome of patients with mild to moderate ulcerative colitis (UC). 

The eight-strain live biotherapeutic product (MB310, Microbiotica) is due to enter its first clinical trial later this year.

In patients with UC who showed clinical benefit after fecal microbiota transplantation (FMT), these eight specific bacterial strains were shown to be consistently elevated, reported Ron Carter, MD, chief medical officer at Microbiotica, Cambridge, UK, the company developing the product. 

In addition, “in lab studies, we’ve found they exhibit anti-inflammatory effects when incubated with different cells of the immune system,” he explained. With the biotherapeutic product, “we want to prompt the immune system to realign the gut inflammation” in UC.

On February 23, at the annual congress of the European Crohn’s and Colitis Organisation, Dr. Carter presented the work-to-date and the near-term plans for a phase 1b randomized, placebo-controlled, double-blind trial to be conducted across roughly 20 sites in Europe (Abstract DOP 67). The trial, COMPOSER-1, will investigate the engraftment and initial signs of clinical activity of MB310 in 30 patients with active, mild to moderate UC (modified Mayo score 4-7; endoscopic subscore ≥ 2).

 Calming Inflammation With Specific Bacteria 

To date, the researchers have focused on identifying bacterial species that correlate with clinical outcomes in individual patients with UC after treatment with FMT. Dr. Carter and colleagues worked in collaboration with Sam Costello, MBBS, gastroenterologist at The Queen Elizabeth Hospital in Adelaide, Australia.

The initial research involved analyzing stool samples from a round 70 patients diagnosed with mild to moderate UC, who were randomly assigned to receive either pooled, anaerobically prepared, healthy donor FMT, or their own autologous FMT as a comparative control. FMT was delivered via colonoscopy and two enemas over 7 days. The primary endpoint of the study was achieving steroid-free remission of UC on the basis of specific Mayo scores, at the end of week 8.

“Results indicated that the group receiving the pooled donor FMT showed a 32% success rate with respect to the primary outcome compared with only 9% of the control group,” said Dr. Carter. “This suggested a promising therapeutic strategy.”

Based on these outcomes, Microbiotica then decided to conduct a local study in which they analyzed fecal samples from FMT donors and from pre-FMT and post-FMT recipients in order to precisely identify which bacterial species were associated with clinical response. 

“With our precision microbiome analysis platform, we determined eight bacterial species that were consistently elevated in FMT responders, but absent or not elevated in non-responders,” reported Dr. Carter.

Next, they carried out subspecies-level bioinformatic analysis and identified one bacterial strain from each of the eight species, which were then cultured individually, freeze-dried, and combined into a custom delayed-release capsule. 

The researchers tested the resulting live biotherapeutic product in cellular assays using human cell lines to confirm that they effectively modulated immune functions. 

The cellular assays showed that in epithelial cell monolayer tests, MB310 not only enhanced barrier integrity but also protected the cellular barrier from inflammation. 

The eight bacterial strain combination also exhibited anti-inflammatory effects when incubated with different primary innate immune cells, dendritic cells, and M1 macrophages. 

And, Dr. Carter emphasized, the specific MB310 bacterial strains were found to regulate T-cells directly or via metabolites.

Moving in the Right Direction

Julien Kirchgesner, MD, Saint-Antoine Hospital and Sorbonne University, Paris, France, who co-moderated the session where the research was presented, welcomed the work.

“Many more trials need to be done before we see this enter the clinic, but this is moving in the right direction,” Dr. Kirchgesner noted.

“We need to find only the functionally active bacterial strains, rather than just take the fecal transplant alone [as is done with FMT],” he said. That is what is being done here.

“The researchers want to identify which bacterial strains will impact the effectiveness in patients, and to select for these strains before industrializing the process and producing them at the optimal strength, at scale,” Dr. Kirchgesner said.

Dr. Carter is chief medical officer at Microbiotica and Dr Kirshgensner has no financial disclosures.

A version of this article appeared on Medscape.com.

While TikTok overflows with images of influencers making “adrenal cocktails” to combat what they call adrenal fatigue, the Endocrine Society says “no scientific proof exists to support adrenal fatigue as a true medical condition.”

Even before influencers began touting it on social media, a 2016 systematic review concluded that there is “no substantiation that adrenal fatigue” is an actual medical condition. Therefore, adrenal fatigue is still a myth.

Lynette Nieman, MD, Senior Investigator and Chief of the Endocrinology Consultation Service at the National Institutes of Health Clinical Center, Bethesda, Maryland, concurs.

“There is no scientific evidence that adrenal fatigue exists or causes [general] fatigue, depression, or the many common symptoms that are said to result from this condition,” she told this news organization via email.

Still, the term has gained currency among not only social media influencers who blame it for everything from cortisol surges to estrogen imbalances but also functional and integrative medical practitioners as an explanation for chronic dysfunction related to stress. 
 

Adrenal Fatigue, Burnout, or Adrenal Insufficiency?

Rather than “adrenal fatigue,” Marcelo Campos, MD, a primary care doctor at Atrius Health, said he prefers the medical term “burnout.”

Use of “burnout” shifts attention to the brain’s role in stress-related chronic dysfunction rather than the adrenal glands, said Dr. Campos, who also teaches at Harvard Medical School, Cambridge, Massachusetts.

More specifically still, the focuses might shift to the stress-response via the hypothalamic-pituitary-adrenocortical axis and its role in reducing levels of these cortisol and dehydroepiandrosterone sulfate.

He points out that part of the reason for the misuse of the term adrenal fatigue arises from the fact that burnout is often only associated with work stress.

“Recently, the ICD-11 [International Classification of Diseases-11] recognized burnout as a disease but focused only on work stress as a cause. The truth is that people can be burned out for many other reasons,” said Dr. Campos.

The Endocrine Society notes on their webpage dedicated to the topic that “adrenal fatigue” as a term, relates to long-term mental, emotional, or physical stress.

“The problem is not the adrenals — it is the exposure to stress in the brain. The brain — only one organ — is responsible for 40% of energy consumption in the body. As you can imagine, if you are under constant stress, you run out of gas very quickly and cannot function well,” he explained.

Adrenal fatigue theory suggests that, under stress, the adrenal glands produce too many short bursts of cortisol resulting in overall reduced cortisol levels and a feeling of being drained.

“As with many other psychiatric diseases, we do not have a way to measure biomarkers in the brain. The testing for cortisol does not work because it fluctuates too much from time to time. So, it is not reliable or reproducible,” Dr. Campos said. 

This leads to the ongoing question of the best way to test and diagnose adrenal fatigue, whether it should be via blood, urine and/or saliva. And even if that is determined, there are still questions about the best time to test, how often, what the normal ranges are and how reliable the tests are.

While adrenal fatigue is not a recognized condition, adrenal insufficiency is medically recognized, resulting from an inability of the adrenal glands to make the life-essential hormones aldosterone and/or cortisol, with symptoms that include fatigue, belly pain, nausea, vomiting, diarrhea, and joint aches.

“Adrenal cocktails are not an effective treatment for adrenal insufficiency because they do not replace the missing hormones,” Dr. Nieman stated, pointing out that anyone with symptoms of adrenal insufficiency needs to see an endocrinologist.

Pratibha Rao, MD, MPH, an endocrinologist at the Cleveland Clinic, Ohio, and medical director of the Adrenal Center at Cleveland Clinic, agreed, advising that if people continue to feel exhausted beyond their normal exertion, then they should get checked for signs of adrenal insufficiency.

“In primary adrenal insufficiency, you can actually start seeing darkening of the gums and of the skin on the palms of the hands or the soles of your feet. Sometimes people can feel dizzy or experience some loss of consciousness,” she said. “If it’s sudden and severe, you may crave salt or have extreme heat or cold intolerance.”

Recognizing and Managing Patient Frustration

The lack of formal diagnostic criteria and medical evidence, however, doesn’t mean that such symptoms as fatigue and depression don’t present, often causing significant distress for patients. While the symptoms might not be associated with the adrenal glands, they still need addressing — but how that is done is, in essence, a bone of contention.

Dr. Rao empathizes with the situation that many people, often young women, find themselves in.

“Patients are frustrated. They’ve gone to multiple doctors across the country, and they feel convinced they have adrenal fatigue, but no medical doctor has endorsed it. They end up coming to us with a cry that has so often gone unanswered.”

This issue also highlights that there are millions of people experiencing mental, emotional, and physical distress of unknown cause who seek help, many of whom believe it is related to their adrenal gland function.

But rather than turning to a social media cure, Dr. Rao stresses that people would benefit more from paying greater attention to following a healthy lifestyle than regularly consuming sugar-rich drinks claimed to offer a solution. Adrenal cocktails are energy-rich, frothy blends of orange juice, coconut milk, cream of tartar, and Himalayan salt.

“We truly are what we eat, and we are what we think,” she noted.

The body is a miraculous machine, but “we forget that it does need maintenance,” Dr. Rao said. “Up to age 30, the body is so forgiving with drugs, alcohol, or whatever insult we do to it, but after the third decade, slowly every cell starts to degenerate instead of growing. We start to see the ill or beneficial effects of lifestyle habits.” 

“We insult the body, and then we say, ‘oh, I have fatigue’ and seek a quick fix,” she added. “Everyone wants instant gratification.”

Dr. Rao cautioned that adrenal cocktails could be dangerous for someone who has other medical conditions.

“If someone has kidney disease, uncontrolled hypertension, or diabetes, for example, then adrenal cocktails are definitely not safe,” Dr. Rao said. “Loading up with potassium and sodium, which is found in high quantities in adrenal cocktails, will actually worsen any kidney damage, while consuming so much sugar will cause an unregulated rise in blood sugar and further damage in someone with diabetes.”

Dr. Rao also stressed that nonprofessional advice given on social media could take patient people down the wrong path with associated danger.

A version of this article appeared on Medscape.com.

While TikTok overflows with images of influencers making “adrenal cocktails” to combat what they call adrenal fatigue, the Endocrine Society says “no scientific proof exists to support adrenal fatigue as a true medical condition.”

Even before influencers began touting it on social media, a 2016 systematic review concluded that there is “no substantiation that adrenal fatigue” is an actual medical condition. Therefore, adrenal fatigue is still a myth.

Lynette Nieman, MD, Senior Investigator and Chief of the Endocrinology Consultation Service at the National Institutes of Health Clinical Center, Bethesda, Maryland, concurs.

“There is no scientific evidence that adrenal fatigue exists or causes [general] fatigue, depression, or the many common symptoms that are said to result from this condition,” she told this news organization via email.

Still, the term has gained currency among not only social media influencers who blame it for everything from cortisol surges to estrogen imbalances but also functional and integrative medical practitioners as an explanation for chronic dysfunction related to stress. 
 

Adrenal Fatigue, Burnout, or Adrenal Insufficiency?

Rather than “adrenal fatigue,” Marcelo Campos, MD, a primary care doctor at Atrius Health, said he prefers the medical term “burnout.”

Use of “burnout” shifts attention to the brain’s role in stress-related chronic dysfunction rather than the adrenal glands, said Dr. Campos, who also teaches at Harvard Medical School, Cambridge, Massachusetts.

More specifically still, the focuses might shift to the stress-response via the hypothalamic-pituitary-adrenocortical axis and its role in reducing levels of these cortisol and dehydroepiandrosterone sulfate.

He points out that part of the reason for the misuse of the term adrenal fatigue arises from the fact that burnout is often only associated with work stress.

“Recently, the ICD-11 [International Classification of Diseases-11] recognized burnout as a disease but focused only on work stress as a cause. The truth is that people can be burned out for many other reasons,” said Dr. Campos.

The Endocrine Society notes on their webpage dedicated to the topic that “adrenal fatigue” as a term, relates to long-term mental, emotional, or physical stress.

“The problem is not the adrenals — it is the exposure to stress in the brain. The brain — only one organ — is responsible for 40% of energy consumption in the body. As you can imagine, if you are under constant stress, you run out of gas very quickly and cannot function well,” he explained.

Adrenal fatigue theory suggests that, under stress, the adrenal glands produce too many short bursts of cortisol resulting in overall reduced cortisol levels and a feeling of being drained.

“As with many other psychiatric diseases, we do not have a way to measure biomarkers in the brain. The testing for cortisol does not work because it fluctuates too much from time to time. So, it is not reliable or reproducible,” Dr. Campos said. 

This leads to the ongoing question of the best way to test and diagnose adrenal fatigue, whether it should be via blood, urine and/or saliva. And even if that is determined, there are still questions about the best time to test, how often, what the normal ranges are and how reliable the tests are.

While adrenal fatigue is not a recognized condition, adrenal insufficiency is medically recognized, resulting from an inability of the adrenal glands to make the life-essential hormones aldosterone and/or cortisol, with symptoms that include fatigue, belly pain, nausea, vomiting, diarrhea, and joint aches.

“Adrenal cocktails are not an effective treatment for adrenal insufficiency because they do not replace the missing hormones,” Dr. Nieman stated, pointing out that anyone with symptoms of adrenal insufficiency needs to see an endocrinologist.

Pratibha Rao, MD, MPH, an endocrinologist at the Cleveland Clinic, Ohio, and medical director of the Adrenal Center at Cleveland Clinic, agreed, advising that if people continue to feel exhausted beyond their normal exertion, then they should get checked for signs of adrenal insufficiency.

“In primary adrenal insufficiency, you can actually start seeing darkening of the gums and of the skin on the palms of the hands or the soles of your feet. Sometimes people can feel dizzy or experience some loss of consciousness,” she said. “If it’s sudden and severe, you may crave salt or have extreme heat or cold intolerance.”

Recognizing and Managing Patient Frustration

The lack of formal diagnostic criteria and medical evidence, however, doesn’t mean that such symptoms as fatigue and depression don’t present, often causing significant distress for patients. While the symptoms might not be associated with the adrenal glands, they still need addressing — but how that is done is, in essence, a bone of contention.

Dr. Rao empathizes with the situation that many people, often young women, find themselves in.

“Patients are frustrated. They’ve gone to multiple doctors across the country, and they feel convinced they have adrenal fatigue, but no medical doctor has endorsed it. They end up coming to us with a cry that has so often gone unanswered.”

This issue also highlights that there are millions of people experiencing mental, emotional, and physical distress of unknown cause who seek help, many of whom believe it is related to their adrenal gland function.

But rather than turning to a social media cure, Dr. Rao stresses that people would benefit more from paying greater attention to following a healthy lifestyle than regularly consuming sugar-rich drinks claimed to offer a solution. Adrenal cocktails are energy-rich, frothy blends of orange juice, coconut milk, cream of tartar, and Himalayan salt.

“We truly are what we eat, and we are what we think,” she noted.

The body is a miraculous machine, but “we forget that it does need maintenance,” Dr. Rao said. “Up to age 30, the body is so forgiving with drugs, alcohol, or whatever insult we do to it, but after the third decade, slowly every cell starts to degenerate instead of growing. We start to see the ill or beneficial effects of lifestyle habits.” 

“We insult the body, and then we say, ‘oh, I have fatigue’ and seek a quick fix,” she added. “Everyone wants instant gratification.”

Dr. Rao cautioned that adrenal cocktails could be dangerous for someone who has other medical conditions.

“If someone has kidney disease, uncontrolled hypertension, or diabetes, for example, then adrenal cocktails are definitely not safe,” Dr. Rao said. “Loading up with potassium and sodium, which is found in high quantities in adrenal cocktails, will actually worsen any kidney damage, while consuming so much sugar will cause an unregulated rise in blood sugar and further damage in someone with diabetes.”

Dr. Rao also stressed that nonprofessional advice given on social media could take patient people down the wrong path with associated danger.

A version of this article appeared on Medscape.com.

While TikTok overflows with images of influencers making “adrenal cocktails” to combat what they call adrenal fatigue, the Endocrine Society says “no scientific proof exists to support adrenal fatigue as a true medical condition.”

Even before influencers began touting it on social media, a 2016 systematic review concluded that there is “no substantiation that adrenal fatigue” is an actual medical condition. Therefore, adrenal fatigue is still a myth.

Lynette Nieman, MD, Senior Investigator and Chief of the Endocrinology Consultation Service at the National Institutes of Health Clinical Center, Bethesda, Maryland, concurs.

“There is no scientific evidence that adrenal fatigue exists or causes [general] fatigue, depression, or the many common symptoms that are said to result from this condition,” she told this news organization via email.

Still, the term has gained currency among not only social media influencers who blame it for everything from cortisol surges to estrogen imbalances but also functional and integrative medical practitioners as an explanation for chronic dysfunction related to stress. 
 

Adrenal Fatigue, Burnout, or Adrenal Insufficiency?

Rather than “adrenal fatigue,” Marcelo Campos, MD, a primary care doctor at Atrius Health, said he prefers the medical term “burnout.”

Use of “burnout” shifts attention to the brain’s role in stress-related chronic dysfunction rather than the adrenal glands, said Dr. Campos, who also teaches at Harvard Medical School, Cambridge, Massachusetts.

More specifically still, the focuses might shift to the stress-response via the hypothalamic-pituitary-adrenocortical axis and its role in reducing levels of these cortisol and dehydroepiandrosterone sulfate.

He points out that part of the reason for the misuse of the term adrenal fatigue arises from the fact that burnout is often only associated with work stress.

“Recently, the ICD-11 [International Classification of Diseases-11] recognized burnout as a disease but focused only on work stress as a cause. The truth is that people can be burned out for many other reasons,” said Dr. Campos.

The Endocrine Society notes on their webpage dedicated to the topic that “adrenal fatigue” as a term, relates to long-term mental, emotional, or physical stress.

“The problem is not the adrenals — it is the exposure to stress in the brain. The brain — only one organ — is responsible for 40% of energy consumption in the body. As you can imagine, if you are under constant stress, you run out of gas very quickly and cannot function well,” he explained.

Adrenal fatigue theory suggests that, under stress, the adrenal glands produce too many short bursts of cortisol resulting in overall reduced cortisol levels and a feeling of being drained.

“As with many other psychiatric diseases, we do not have a way to measure biomarkers in the brain. The testing for cortisol does not work because it fluctuates too much from time to time. So, it is not reliable or reproducible,” Dr. Campos said. 

This leads to the ongoing question of the best way to test and diagnose adrenal fatigue, whether it should be via blood, urine and/or saliva. And even if that is determined, there are still questions about the best time to test, how often, what the normal ranges are and how reliable the tests are.

While adrenal fatigue is not a recognized condition, adrenal insufficiency is medically recognized, resulting from an inability of the adrenal glands to make the life-essential hormones aldosterone and/or cortisol, with symptoms that include fatigue, belly pain, nausea, vomiting, diarrhea, and joint aches.

“Adrenal cocktails are not an effective treatment for adrenal insufficiency because they do not replace the missing hormones,” Dr. Nieman stated, pointing out that anyone with symptoms of adrenal insufficiency needs to see an endocrinologist.

Pratibha Rao, MD, MPH, an endocrinologist at the Cleveland Clinic, Ohio, and medical director of the Adrenal Center at Cleveland Clinic, agreed, advising that if people continue to feel exhausted beyond their normal exertion, then they should get checked for signs of adrenal insufficiency.

“In primary adrenal insufficiency, you can actually start seeing darkening of the gums and of the skin on the palms of the hands or the soles of your feet. Sometimes people can feel dizzy or experience some loss of consciousness,” she said. “If it’s sudden and severe, you may crave salt or have extreme heat or cold intolerance.”

Recognizing and Managing Patient Frustration

The lack of formal diagnostic criteria and medical evidence, however, doesn’t mean that such symptoms as fatigue and depression don’t present, often causing significant distress for patients. While the symptoms might not be associated with the adrenal glands, they still need addressing — but how that is done is, in essence, a bone of contention.

Dr. Rao empathizes with the situation that many people, often young women, find themselves in.

“Patients are frustrated. They’ve gone to multiple doctors across the country, and they feel convinced they have adrenal fatigue, but no medical doctor has endorsed it. They end up coming to us with a cry that has so often gone unanswered.”

This issue also highlights that there are millions of people experiencing mental, emotional, and physical distress of unknown cause who seek help, many of whom believe it is related to their adrenal gland function.

But rather than turning to a social media cure, Dr. Rao stresses that people would benefit more from paying greater attention to following a healthy lifestyle than regularly consuming sugar-rich drinks claimed to offer a solution. Adrenal cocktails are energy-rich, frothy blends of orange juice, coconut milk, cream of tartar, and Himalayan salt.

“We truly are what we eat, and we are what we think,” she noted.

The body is a miraculous machine, but “we forget that it does need maintenance,” Dr. Rao said. “Up to age 30, the body is so forgiving with drugs, alcohol, or whatever insult we do to it, but after the third decade, slowly every cell starts to degenerate instead of growing. We start to see the ill or beneficial effects of lifestyle habits.” 

“We insult the body, and then we say, ‘oh, I have fatigue’ and seek a quick fix,” she added. “Everyone wants instant gratification.”

Dr. Rao cautioned that adrenal cocktails could be dangerous for someone who has other medical conditions.

“If someone has kidney disease, uncontrolled hypertension, or diabetes, for example, then adrenal cocktails are definitely not safe,” Dr. Rao said. “Loading up with potassium and sodium, which is found in high quantities in adrenal cocktails, will actually worsen any kidney damage, while consuming so much sugar will cause an unregulated rise in blood sugar and further damage in someone with diabetes.”

Dr. Rao also stressed that nonprofessional advice given on social media could take patient people down the wrong path with associated danger.

A version of this article appeared on Medscape.com.

STOCKHOLM — Long-term data on risankizumab (Skyrizi) in moderate to severe Crohn’s disease (CD) show that clinical remission and endoscopic response rates remain stable for up to 3 years, according to results of the FORTIFY extension study.

“For me, most striking are the endoscopic endpoints,” Marc Ferrante, MD, PhD, AGAF, said in an interview. In the most conservative analysis, “you see a benefit the longer you follow the patients ... We haven’t seen this with many — if any — other compounds before.”

Dr. Ferrante, from University Hospitals Leuven in Belgium, added that patients showed less antibody formation in response to risankizumab, an anti-interleukin (IL)–23 p19 inhibitor, compared with anti–tumor necrosis factor agents. 

Ferrante_Marc_BELGIUM_web.jpg

“Most patients seemed to continue on treatment without the formation of antibodies to risankizumab becoming a problem,” he said. Also, for patients who achieve a good response to risankizumab, the effects were the same whether “they received this biologic first line, or only after failing other compounds.”

Generally, “I think we all have the impression that the IL-23 inhibitors have good efficacy, probably even better than other compounds available,” said Dr. Ferrante. “And, importantly, this is true without any increased adverse effects.”

“Now, with these new long-term data in risankizumab, we see the benefit-risk ratio continues to be favorable,” he added.

Dr. Ferrante presented the data (Abstract DOP 53) on February 23 at the annual congress of the European Crohn’s and Colitis Organisation.
 

Open-Label Extension up to 152 Weeks

The ongoing FORTIFY maintenance open-label extension study is evaluating the long-term efficacy and safety of risankizumab in patients with moderate to severe CD. 

These data follow the initial 52-week study published in 2022 showing that subcutaneous risankizumab was a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active CD. Dr. Ferrante also led that study.

Participants in this open-label extension study who had already completed 52-weeks maintenance dosing received 180-mg subcutaneous risankizumab every 8 weeks (n = 872) at week 56. Those who had received prior rescue therapy, a single 1200-mg intravenous risankizumab dose followed by 360-mg subcutaneously every 8 weeks, continued with this latter regimen (n = 275). Data for analysis were pooled from both treatment groups (risankizumab 180 mg and 360 mg), and clinical outcomes were evaluated every 6 months. 

Data for the population, after patients who received rescue treatment were imputed as nonresponders, showed Clinical Disease Activity Index (CDAI) clinical response of 84.9% at week 56 and 52.7% at week 152. CDAI clinical remission was 66.7% at week 56 and 47.2% at week 152 for this population. 

For endoscopic outcomes, additional benefit was seen over time. Endoscopic response, considered to be the best available predictor of long-term outcomes, was 50.8% at week 56 and 52.5% at week 152. Endoscopic remission was 35.8% at week 56 and 41.8% at week 152, and ulcer-free endoscopy was seen in 28.6% patients at week 56 and 35.5% at week 152.

The safety profile of risankizumab is consistent and supports long-term treatment, Dr. Ferrante said. 

Treatment emergent adverse events included major adverse cardiovascular events in five patients on risankizumab and 50 serious infections.
 

‘Effective and Durable Option’

Providing comment, Tim Raine, MD, a consultant gastroenterologist & IBD lead at Cambridge University Hospitals, United Kingdom, remarked on the value of long-term extension studies for understanding the impact of continued drug administration beyond the typical 1-year time horizon of registrational clinical trials given that CD is currently incurable.

“However, there are limitations with long-term extension studies,” he said in an interview. In particular, the patients who remain in the study tend to be “those who have had a good experience with the drug and remain motivated to take part in ongoing monitoring.” 

But “patients will drop out of a long-term extension study for reasons that may or may not reflect loss of benefit from the drug, and this can be problematic with handling of missing data,” he explained.

In light of this issue, “the investigators have used the most stringent way of handling these patients, regarding all who drop out as instances of failure of the drug. This offers the most robust assessment of durability of response that may slightly underestimate the true long-term efficacy,” said Dr. Raine. 

“Nevertheless, the response and remission rates for clinical endpoints suggest good durability of effect out to 3 years of follow-up. The endoscopic data are also encouraging,” he asserted. 

“Taken together, these data suggest that risankizumab can offer an effective and durable option for some patients with Crohn’s disease and is associated with a favorable safety profile.”

Dr. Ferrante disclosed ties with AbbVie, Agomab Therapeutics, Amgen, Biogen, Boehringer Ingelheim, Celgene, Celltrion, EG, Eli Lilly, Falk, Ferring, Janssen, Janssen-Cilag, Lamepro, Medtronic, MRM, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda, ThermoFisher, Truvion Healthcare, and Viatris. Dr. Raine disclosed ties with AbbVie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Celgene, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Sandoz, Takeda, and UCB.

A version of this article appeared on Medscape.com.

STOCKHOLM — Long-term data on risankizumab (Skyrizi) in moderate to severe Crohn’s disease (CD) show that clinical remission and endoscopic response rates remain stable for up to 3 years, according to results of the FORTIFY extension study.

“For me, most striking are the endoscopic endpoints,” Marc Ferrante, MD, PhD, AGAF, said in an interview. In the most conservative analysis, “you see a benefit the longer you follow the patients ... We haven’t seen this with many — if any — other compounds before.”

Dr. Ferrante, from University Hospitals Leuven in Belgium, added that patients showed less antibody formation in response to risankizumab, an anti-interleukin (IL)–23 p19 inhibitor, compared with anti–tumor necrosis factor agents. 

Ferrante_Marc_BELGIUM_web.jpg

“Most patients seemed to continue on treatment without the formation of antibodies to risankizumab becoming a problem,” he said. Also, for patients who achieve a good response to risankizumab, the effects were the same whether “they received this biologic first line, or only after failing other compounds.”

Generally, “I think we all have the impression that the IL-23 inhibitors have good efficacy, probably even better than other compounds available,” said Dr. Ferrante. “And, importantly, this is true without any increased adverse effects.”

“Now, with these new long-term data in risankizumab, we see the benefit-risk ratio continues to be favorable,” he added.

Dr. Ferrante presented the data (Abstract DOP 53) on February 23 at the annual congress of the European Crohn’s and Colitis Organisation.
 

Open-Label Extension up to 152 Weeks

The ongoing FORTIFY maintenance open-label extension study is evaluating the long-term efficacy and safety of risankizumab in patients with moderate to severe CD. 

These data follow the initial 52-week study published in 2022 showing that subcutaneous risankizumab was a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active CD. Dr. Ferrante also led that study.

Participants in this open-label extension study who had already completed 52-weeks maintenance dosing received 180-mg subcutaneous risankizumab every 8 weeks (n = 872) at week 56. Those who had received prior rescue therapy, a single 1200-mg intravenous risankizumab dose followed by 360-mg subcutaneously every 8 weeks, continued with this latter regimen (n = 275). Data for analysis were pooled from both treatment groups (risankizumab 180 mg and 360 mg), and clinical outcomes were evaluated every 6 months. 

Data for the population, after patients who received rescue treatment were imputed as nonresponders, showed Clinical Disease Activity Index (CDAI) clinical response of 84.9% at week 56 and 52.7% at week 152. CDAI clinical remission was 66.7% at week 56 and 47.2% at week 152 for this population. 

For endoscopic outcomes, additional benefit was seen over time. Endoscopic response, considered to be the best available predictor of long-term outcomes, was 50.8% at week 56 and 52.5% at week 152. Endoscopic remission was 35.8% at week 56 and 41.8% at week 152, and ulcer-free endoscopy was seen in 28.6% patients at week 56 and 35.5% at week 152.

The safety profile of risankizumab is consistent and supports long-term treatment, Dr. Ferrante said. 

Treatment emergent adverse events included major adverse cardiovascular events in five patients on risankizumab and 50 serious infections.
 

‘Effective and Durable Option’

Providing comment, Tim Raine, MD, a consultant gastroenterologist & IBD lead at Cambridge University Hospitals, United Kingdom, remarked on the value of long-term extension studies for understanding the impact of continued drug administration beyond the typical 1-year time horizon of registrational clinical trials given that CD is currently incurable.

“However, there are limitations with long-term extension studies,” he said in an interview. In particular, the patients who remain in the study tend to be “those who have had a good experience with the drug and remain motivated to take part in ongoing monitoring.” 

But “patients will drop out of a long-term extension study for reasons that may or may not reflect loss of benefit from the drug, and this can be problematic with handling of missing data,” he explained.

In light of this issue, “the investigators have used the most stringent way of handling these patients, regarding all who drop out as instances of failure of the drug. This offers the most robust assessment of durability of response that may slightly underestimate the true long-term efficacy,” said Dr. Raine. 

“Nevertheless, the response and remission rates for clinical endpoints suggest good durability of effect out to 3 years of follow-up. The endoscopic data are also encouraging,” he asserted. 

“Taken together, these data suggest that risankizumab can offer an effective and durable option for some patients with Crohn’s disease and is associated with a favorable safety profile.”

Dr. Ferrante disclosed ties with AbbVie, Agomab Therapeutics, Amgen, Biogen, Boehringer Ingelheim, Celgene, Celltrion, EG, Eli Lilly, Falk, Ferring, Janssen, Janssen-Cilag, Lamepro, Medtronic, MRM, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda, ThermoFisher, Truvion Healthcare, and Viatris. Dr. Raine disclosed ties with AbbVie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Celgene, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Sandoz, Takeda, and UCB.

A version of this article appeared on Medscape.com.

STOCKHOLM — Long-term data on risankizumab (Skyrizi) in moderate to severe Crohn’s disease (CD) show that clinical remission and endoscopic response rates remain stable for up to 3 years, according to results of the FORTIFY extension study.

“For me, most striking are the endoscopic endpoints,” Marc Ferrante, MD, PhD, AGAF, said in an interview. In the most conservative analysis, “you see a benefit the longer you follow the patients ... We haven’t seen this with many — if any — other compounds before.”

Dr. Ferrante, from University Hospitals Leuven in Belgium, added that patients showed less antibody formation in response to risankizumab, an anti-interleukin (IL)–23 p19 inhibitor, compared with anti–tumor necrosis factor agents. 

Ferrante_Marc_BELGIUM_web.jpg

“Most patients seemed to continue on treatment without the formation of antibodies to risankizumab becoming a problem,” he said. Also, for patients who achieve a good response to risankizumab, the effects were the same whether “they received this biologic first line, or only after failing other compounds.”

Generally, “I think we all have the impression that the IL-23 inhibitors have good efficacy, probably even better than other compounds available,” said Dr. Ferrante. “And, importantly, this is true without any increased adverse effects.”

“Now, with these new long-term data in risankizumab, we see the benefit-risk ratio continues to be favorable,” he added.

Dr. Ferrante presented the data (Abstract DOP 53) on February 23 at the annual congress of the European Crohn’s and Colitis Organisation.
 

Open-Label Extension up to 152 Weeks

The ongoing FORTIFY maintenance open-label extension study is evaluating the long-term efficacy and safety of risankizumab in patients with moderate to severe CD. 

These data follow the initial 52-week study published in 2022 showing that subcutaneous risankizumab was a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active CD. Dr. Ferrante also led that study.

Participants in this open-label extension study who had already completed 52-weeks maintenance dosing received 180-mg subcutaneous risankizumab every 8 weeks (n = 872) at week 56. Those who had received prior rescue therapy, a single 1200-mg intravenous risankizumab dose followed by 360-mg subcutaneously every 8 weeks, continued with this latter regimen (n = 275). Data for analysis were pooled from both treatment groups (risankizumab 180 mg and 360 mg), and clinical outcomes were evaluated every 6 months. 

Data for the population, after patients who received rescue treatment were imputed as nonresponders, showed Clinical Disease Activity Index (CDAI) clinical response of 84.9% at week 56 and 52.7% at week 152. CDAI clinical remission was 66.7% at week 56 and 47.2% at week 152 for this population. 

For endoscopic outcomes, additional benefit was seen over time. Endoscopic response, considered to be the best available predictor of long-term outcomes, was 50.8% at week 56 and 52.5% at week 152. Endoscopic remission was 35.8% at week 56 and 41.8% at week 152, and ulcer-free endoscopy was seen in 28.6% patients at week 56 and 35.5% at week 152.

The safety profile of risankizumab is consistent and supports long-term treatment, Dr. Ferrante said. 

Treatment emergent adverse events included major adverse cardiovascular events in five patients on risankizumab and 50 serious infections.
 

‘Effective and Durable Option’

Providing comment, Tim Raine, MD, a consultant gastroenterologist & IBD lead at Cambridge University Hospitals, United Kingdom, remarked on the value of long-term extension studies for understanding the impact of continued drug administration beyond the typical 1-year time horizon of registrational clinical trials given that CD is currently incurable.

“However, there are limitations with long-term extension studies,” he said in an interview. In particular, the patients who remain in the study tend to be “those who have had a good experience with the drug and remain motivated to take part in ongoing monitoring.” 

But “patients will drop out of a long-term extension study for reasons that may or may not reflect loss of benefit from the drug, and this can be problematic with handling of missing data,” he explained.

In light of this issue, “the investigators have used the most stringent way of handling these patients, regarding all who drop out as instances of failure of the drug. This offers the most robust assessment of durability of response that may slightly underestimate the true long-term efficacy,” said Dr. Raine. 

“Nevertheless, the response and remission rates for clinical endpoints suggest good durability of effect out to 3 years of follow-up. The endoscopic data are also encouraging,” he asserted. 

“Taken together, these data suggest that risankizumab can offer an effective and durable option for some patients with Crohn’s disease and is associated with a favorable safety profile.”

Dr. Ferrante disclosed ties with AbbVie, Agomab Therapeutics, Amgen, Biogen, Boehringer Ingelheim, Celgene, Celltrion, EG, Eli Lilly, Falk, Ferring, Janssen, Janssen-Cilag, Lamepro, Medtronic, MRM, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda, ThermoFisher, Truvion Healthcare, and Viatris. Dr. Raine disclosed ties with AbbVie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Celgene, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Sandoz, Takeda, and UCB.

A version of this article appeared on Medscape.com.

STOCKHOLM — A proactive treat-to-target strategy in patients with Crohn’s disease (CD) who are in remission but are considered to be high risk as determined by video capsule endoscopy was superior for prevention of clinical flare within the next 2 years compared with continued standard care, a new study showed.

Capsule endoscopy reveals small-intestinal inflammation in over 70% of patients with CD who are in clinical remission, said Shomron Ben-Horin, MD, from Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel. The question remains however, which patients would benefit from treatment intensification. 

The randomized controlled CURE-CD trial showed that patients who have high inflammatory activity — a Lewis score ≥ 350 as seen in video capsule endoscopy findings — experienced statistically significantly fewer relapses during the 2-year follow-up vs patients with the same amount of inflammation who continued their standard treatment, he said.

Dr. Ben-Horin presented the results at the annual congress of the European Crohn’s and Colitis Organisation on behalf of the Israeli IBD Research Nucleus. 

He and his colleagues aimed to examine the value of video capsule endoscopy to guide proactive treat-to-target strategy in patients with CD who are in clinical remission, adding onto their previous work published in 2019 that established the benefit of video capsule endoscopy over calprotectin in predicting relapse. 

The prospective randomized controlled trial recruited 60 patients with CD involving the small bowel who were in clinical remission (Crohn’s Disease Activity Index [CDAI] < 150). Patients underwent clinical, biomarker, and imaging checks as well as video capsule endoscopies at baseline and every 6 months thereafter for up to 24 months. 

A total of 40 patients with a Lewis score ≥ 350 and who were considered high-risk were randomized to either proactive treatment optimization (targeting video capsule endoscopy mucosal healing, n = 20) or to continued standard care (n = 20) for 24 months. Patients with a Lewis score < 350 who were considered to be low-risk continued standard care (n = 20) which may or may not have been biologic. 

The primary outcome was the rate of clinical relapse (disease exacerbation comprised of a CDAI increase > 70 points or hospitalization/surgery) by 24 months in high-risk patients who received standard care vs proactive care. 

Secondary outcomes included risk for flare in the low-risk group (all on standard care) vs the high-risk group also on standard care, predictive profiles for flare of calprotectin, MRI, intestinal ultrasound, and Lewis score over the 24 months. 
 

A Nearly Threefold Difference

Treatment intensification in the high-risk proactive strategy group was split between therapeutic drug monitoring–based biologic dose-escalation (n = 11 in 20), starting a biologic (8 in 20), or swapping a biologic (1 in 20). 

By 24 months, clinical flare occurred in 5 in 20 (25%) of the high-risk proactive group vs 14 (70%) of the high-risk standard-care group (odds ratio [OR], 0.14; 95% CI, 0.04-0.57; P = .006), Dr. Ben-Horin reported. 

The data also showed that low-risk patients had a lower incidence of clinical flare at approximately 45% compared with 70% in high-risk patients also on standard care (P = .11 by intention-to-treat analysis; P = .06 by per-protocol analysis).

In an interview, Dr. Ben-Horin said that despite the results, there remained a “big dilemma” about who should be treated if they show mucosal inflammation on video capsule endoscopy. 

“Crohn’s disease is a progressive disease, and we don’t want flares down the road in a patient that currently feels okay but has underlying inflammation,” he said. “On the other hand, it’s important to consider that our therapies are sometimes associated with adverse events, they can be very costly, and become a huge burden to our healthcare systems and to some of the patients.” 

It is important to ask whether we should or treat patients in remission more aggressively “because not everyone will progress and some of them may never flare,” he explained. 

The findings offer three layers of added evidence to the field, Dr. Ben-Horin said. First, it offers further support to the treat-to-target approach if tailored to a high-risk group. Second, the study suggests that treat-to-target studies should be looking only at the high-risk patients and not the entire study population. “This is the first study of its kind to take this approach,” he pointed out. 

“Thirdly, our results build on our preceding trial to show that using video capsule endoscopy enables us to stratify the risk of patients’ with small-bowel Crohn’s disease and tailor their treatment accordingly, probably more accurately than calprotectin or C-reactive protein.”

Asked to comment on the results, Maria Abreu, MD, AGAF, a gastroenterologist who specializes in inflammatory bowel disease at the University of Miami, Miami, Florida, said that though it was a small study, it highlights that patients need to be closely monitored with objective, quantifiable tests for the best outcomes. 

She continued: “Capsule endoscopy is certainly the most sensitive test we have and lends itself in short order to artificial intelligence interpretation and quantification to make it even more robust.”

“We now need to nuance who needs a capsule vs intestinal ultrasound vs a colonoscopy, and that is likely to depend on disease location and manifestations of the disease,” ie, mucosa-only or transmural-predominant disease, she noted. 

Dr. Ben-Horin has declared that the trial was funded by the Helmsley Charitable Trust. The VCE was partly provided by Medtronic. He disclosed advisory board fees and/or consulting and/or research support from Janssen, AbbVie, CellTrion, Takeda, Schering Plough, Pfizer, Ferring, Falk Pharma, GlaxoSmithKline, Novartis, Roche, Galmed, EviNature, Galmed, PredictaMed, NeoPharm. 

Dr. Abreu has served as a consultant and scientific advisory board member for AbbVie, Arena Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly Pharmaceuticals, Gilead, Janssen Biotech, and Prometheus Biosciences, University of California, Berkeley; a speaker for Alimentiv; and has had projects funded by Pfizer, Prometheus Laboratories, and Takeda Pharmaceuticals.

A version of this article appeared on Medscape.com.

STOCKHOLM — A proactive treat-to-target strategy in patients with Crohn’s disease (CD) who are in remission but are considered to be high risk as determined by video capsule endoscopy was superior for prevention of clinical flare within the next 2 years compared with continued standard care, a new study showed.

Capsule endoscopy reveals small-intestinal inflammation in over 70% of patients with CD who are in clinical remission, said Shomron Ben-Horin, MD, from Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel. The question remains however, which patients would benefit from treatment intensification. 

The randomized controlled CURE-CD trial showed that patients who have high inflammatory activity — a Lewis score ≥ 350 as seen in video capsule endoscopy findings — experienced statistically significantly fewer relapses during the 2-year follow-up vs patients with the same amount of inflammation who continued their standard treatment, he said.

Dr. Ben-Horin presented the results at the annual congress of the European Crohn’s and Colitis Organisation on behalf of the Israeli IBD Research Nucleus. 

He and his colleagues aimed to examine the value of video capsule endoscopy to guide proactive treat-to-target strategy in patients with CD who are in clinical remission, adding onto their previous work published in 2019 that established the benefit of video capsule endoscopy over calprotectin in predicting relapse. 

The prospective randomized controlled trial recruited 60 patients with CD involving the small bowel who were in clinical remission (Crohn’s Disease Activity Index [CDAI] < 150). Patients underwent clinical, biomarker, and imaging checks as well as video capsule endoscopies at baseline and every 6 months thereafter for up to 24 months. 

A total of 40 patients with a Lewis score ≥ 350 and who were considered high-risk were randomized to either proactive treatment optimization (targeting video capsule endoscopy mucosal healing, n = 20) or to continued standard care (n = 20) for 24 months. Patients with a Lewis score < 350 who were considered to be low-risk continued standard care (n = 20) which may or may not have been biologic. 

The primary outcome was the rate of clinical relapse (disease exacerbation comprised of a CDAI increase > 70 points or hospitalization/surgery) by 24 months in high-risk patients who received standard care vs proactive care. 

Secondary outcomes included risk for flare in the low-risk group (all on standard care) vs the high-risk group also on standard care, predictive profiles for flare of calprotectin, MRI, intestinal ultrasound, and Lewis score over the 24 months. 
 

A Nearly Threefold Difference

Treatment intensification in the high-risk proactive strategy group was split between therapeutic drug monitoring–based biologic dose-escalation (n = 11 in 20), starting a biologic (8 in 20), or swapping a biologic (1 in 20). 

By 24 months, clinical flare occurred in 5 in 20 (25%) of the high-risk proactive group vs 14 (70%) of the high-risk standard-care group (odds ratio [OR], 0.14; 95% CI, 0.04-0.57; P = .006), Dr. Ben-Horin reported. 

The data also showed that low-risk patients had a lower incidence of clinical flare at approximately 45% compared with 70% in high-risk patients also on standard care (P = .11 by intention-to-treat analysis; P = .06 by per-protocol analysis).

In an interview, Dr. Ben-Horin said that despite the results, there remained a “big dilemma” about who should be treated if they show mucosal inflammation on video capsule endoscopy. 

“Crohn’s disease is a progressive disease, and we don’t want flares down the road in a patient that currently feels okay but has underlying inflammation,” he said. “On the other hand, it’s important to consider that our therapies are sometimes associated with adverse events, they can be very costly, and become a huge burden to our healthcare systems and to some of the patients.” 

It is important to ask whether we should or treat patients in remission more aggressively “because not everyone will progress and some of them may never flare,” he explained. 

The findings offer three layers of added evidence to the field, Dr. Ben-Horin said. First, it offers further support to the treat-to-target approach if tailored to a high-risk group. Second, the study suggests that treat-to-target studies should be looking only at the high-risk patients and not the entire study population. “This is the first study of its kind to take this approach,” he pointed out. 

“Thirdly, our results build on our preceding trial to show that using video capsule endoscopy enables us to stratify the risk of patients’ with small-bowel Crohn’s disease and tailor their treatment accordingly, probably more accurately than calprotectin or C-reactive protein.”

Asked to comment on the results, Maria Abreu, MD, AGAF, a gastroenterologist who specializes in inflammatory bowel disease at the University of Miami, Miami, Florida, said that though it was a small study, it highlights that patients need to be closely monitored with objective, quantifiable tests for the best outcomes. 

She continued: “Capsule endoscopy is certainly the most sensitive test we have and lends itself in short order to artificial intelligence interpretation and quantification to make it even more robust.”

“We now need to nuance who needs a capsule vs intestinal ultrasound vs a colonoscopy, and that is likely to depend on disease location and manifestations of the disease,” ie, mucosa-only or transmural-predominant disease, she noted. 

Dr. Ben-Horin has declared that the trial was funded by the Helmsley Charitable Trust. The VCE was partly provided by Medtronic. He disclosed advisory board fees and/or consulting and/or research support from Janssen, AbbVie, CellTrion, Takeda, Schering Plough, Pfizer, Ferring, Falk Pharma, GlaxoSmithKline, Novartis, Roche, Galmed, EviNature, Galmed, PredictaMed, NeoPharm. 

Dr. Abreu has served as a consultant and scientific advisory board member for AbbVie, Arena Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly Pharmaceuticals, Gilead, Janssen Biotech, and Prometheus Biosciences, University of California, Berkeley; a speaker for Alimentiv; and has had projects funded by Pfizer, Prometheus Laboratories, and Takeda Pharmaceuticals.

A version of this article appeared on Medscape.com.

STOCKHOLM — A proactive treat-to-target strategy in patients with Crohn’s disease (CD) who are in remission but are considered to be high risk as determined by video capsule endoscopy was superior for prevention of clinical flare within the next 2 years compared with continued standard care, a new study showed.

Capsule endoscopy reveals small-intestinal inflammation in over 70% of patients with CD who are in clinical remission, said Shomron Ben-Horin, MD, from Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel. The question remains however, which patients would benefit from treatment intensification. 

The randomized controlled CURE-CD trial showed that patients who have high inflammatory activity — a Lewis score ≥ 350 as seen in video capsule endoscopy findings — experienced statistically significantly fewer relapses during the 2-year follow-up vs patients with the same amount of inflammation who continued their standard treatment, he said.

Dr. Ben-Horin presented the results at the annual congress of the European Crohn’s and Colitis Organisation on behalf of the Israeli IBD Research Nucleus. 

He and his colleagues aimed to examine the value of video capsule endoscopy to guide proactive treat-to-target strategy in patients with CD who are in clinical remission, adding onto their previous work published in 2019 that established the benefit of video capsule endoscopy over calprotectin in predicting relapse. 

The prospective randomized controlled trial recruited 60 patients with CD involving the small bowel who were in clinical remission (Crohn’s Disease Activity Index [CDAI] < 150). Patients underwent clinical, biomarker, and imaging checks as well as video capsule endoscopies at baseline and every 6 months thereafter for up to 24 months. 

A total of 40 patients with a Lewis score ≥ 350 and who were considered high-risk were randomized to either proactive treatment optimization (targeting video capsule endoscopy mucosal healing, n = 20) or to continued standard care (n = 20) for 24 months. Patients with a Lewis score < 350 who were considered to be low-risk continued standard care (n = 20) which may or may not have been biologic. 

The primary outcome was the rate of clinical relapse (disease exacerbation comprised of a CDAI increase > 70 points or hospitalization/surgery) by 24 months in high-risk patients who received standard care vs proactive care. 

Secondary outcomes included risk for flare in the low-risk group (all on standard care) vs the high-risk group also on standard care, predictive profiles for flare of calprotectin, MRI, intestinal ultrasound, and Lewis score over the 24 months. 
 

A Nearly Threefold Difference

Treatment intensification in the high-risk proactive strategy group was split between therapeutic drug monitoring–based biologic dose-escalation (n = 11 in 20), starting a biologic (8 in 20), or swapping a biologic (1 in 20). 

By 24 months, clinical flare occurred in 5 in 20 (25%) of the high-risk proactive group vs 14 (70%) of the high-risk standard-care group (odds ratio [OR], 0.14; 95% CI, 0.04-0.57; P = .006), Dr. Ben-Horin reported. 

The data also showed that low-risk patients had a lower incidence of clinical flare at approximately 45% compared with 70% in high-risk patients also on standard care (P = .11 by intention-to-treat analysis; P = .06 by per-protocol analysis).

In an interview, Dr. Ben-Horin said that despite the results, there remained a “big dilemma” about who should be treated if they show mucosal inflammation on video capsule endoscopy. 

“Crohn’s disease is a progressive disease, and we don’t want flares down the road in a patient that currently feels okay but has underlying inflammation,” he said. “On the other hand, it’s important to consider that our therapies are sometimes associated with adverse events, they can be very costly, and become a huge burden to our healthcare systems and to some of the patients.” 

It is important to ask whether we should or treat patients in remission more aggressively “because not everyone will progress and some of them may never flare,” he explained. 

The findings offer three layers of added evidence to the field, Dr. Ben-Horin said. First, it offers further support to the treat-to-target approach if tailored to a high-risk group. Second, the study suggests that treat-to-target studies should be looking only at the high-risk patients and not the entire study population. “This is the first study of its kind to take this approach,” he pointed out. 

“Thirdly, our results build on our preceding trial to show that using video capsule endoscopy enables us to stratify the risk of patients’ with small-bowel Crohn’s disease and tailor their treatment accordingly, probably more accurately than calprotectin or C-reactive protein.”

Asked to comment on the results, Maria Abreu, MD, AGAF, a gastroenterologist who specializes in inflammatory bowel disease at the University of Miami, Miami, Florida, said that though it was a small study, it highlights that patients need to be closely monitored with objective, quantifiable tests for the best outcomes. 

She continued: “Capsule endoscopy is certainly the most sensitive test we have and lends itself in short order to artificial intelligence interpretation and quantification to make it even more robust.”

“We now need to nuance who needs a capsule vs intestinal ultrasound vs a colonoscopy, and that is likely to depend on disease location and manifestations of the disease,” ie, mucosa-only or transmural-predominant disease, she noted. 

Dr. Ben-Horin has declared that the trial was funded by the Helmsley Charitable Trust. The VCE was partly provided by Medtronic. He disclosed advisory board fees and/or consulting and/or research support from Janssen, AbbVie, CellTrion, Takeda, Schering Plough, Pfizer, Ferring, Falk Pharma, GlaxoSmithKline, Novartis, Roche, Galmed, EviNature, Galmed, PredictaMed, NeoPharm. 

Dr. Abreu has served as a consultant and scientific advisory board member for AbbVie, Arena Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly Pharmaceuticals, Gilead, Janssen Biotech, and Prometheus Biosciences, University of California, Berkeley; a speaker for Alimentiv; and has had projects funded by Pfizer, Prometheus Laboratories, and Takeda Pharmaceuticals.

A version of this article appeared on Medscape.com.

The oral thyroid hormone receptor beta-selective agonist resmetirom (Madrigal Pharmaceuticals) in both 80-mg and 100-mg doses was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis, according to the results of the ongoing phase 3 MAESTRO-NASH trial published in The New England Journal of Medicine.

Although certain findings from this trial were initially presented at the European Association for the Study of the Liver Congress 2023, the publication of the full peer-reviewed paper represents a potentially significant milestone in the management of NASH, a disease for which there is currently no approved pharmacologic treatment. 

Harrison_Stephen_A_TEXAS_web.jpg

“Data for the first 1,050 patients from the MAESTRO-NASH trial, together with data from completed resmetirom trials, support the potential for resmetirom to provide benefit to patients with NASH and liver fibrosis,” wrote the authors, led by principal investigator Stephen Harrison, MD, chairman of Pinnacle Clinical Research and Summit Clinical Research in San Antonio, Texas. 

The trial uses the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to metabolic dysfunction–associated steatohepatitis (MASH) and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. 
 

A Closer Look at MAESTRO-NASH

Investigators enrolled 996 participants who were randomly assigned to receive placebo or resmetirom at 80 mg or 100 mg. Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score. 

They observed that patients receiving resmetirom had a significant improvement across both doses and both primary endpoints. 

NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, vs 9.7% on placebo. Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the increasing-dose groups, respectively, compared with 14.2% on placebo (P < .001 for both doses compared with placebo). 

The effects with resmetirom were consistent across key subgroups, regardless of baseline fibrosis stage; baseline NAFLD activity score; or type 2 diabetes status, age, and sex. 

“Multiple non-invasive tests for NASH, steatosis, and fibrosis (including blood biomarkers and imaging) showed a similar direction of effects favoring resmetirom treatment, which supports the findings for the primary end points,” Dr. Harrison and colleagues wrote. 

The majority of patients with NASH also have diabetes. As a result, patients with NASH are known to have a high cardiovascular risk and mortality. However, MAESTRO-NASH investigators reported that compared with those receiving placebo, patients on resmetirom experienced reductions in levels of a broad range of atherogenic lipids and lipoproteins, including low-density lipoprotein (LDL) cholesterol, non–high-density lipoprotein cholesterol, triglycerides, apolipoprotein B, and lipoprotein(a). These findings were consistent with earlier studies of resmetirom. 

From baseline to week 24, LDL cholesterol levels were reduced by -13.6% in the 80-mg and by -16.3% in the 100-mg resmetirom groups compared with 0.1% in the placebo group (P < .001).

More patients in the 100-mg group than in the 80-mg or placebo groups discontinued the trial due to adverse events (6.8% vs 1.8% and 2.2%, respectively). Diarrhea and nausea occurred more frequently in the resmetirom groups than in the placebo group. Serious adverse events occurred with similar incidences across the 100-mg, 80-mg, and placebo groups (12.7%, 10.9%, and 11.5%, respectively).

Although to date the MAESTRO-NASH trial lacks clinical outcomes, over its planned duration of 54 months, investigators will accrue data on liver-related outcomes, including progression to cirrhosis. Likewise, long-term safety data will become available with the trial’s completion. 

Disclosure forms provided by the authors are available with the full text of the NEJM paper at NEJM.org. 

A version of this article appeared on Medscape.com.

The oral thyroid hormone receptor beta-selective agonist resmetirom (Madrigal Pharmaceuticals) in both 80-mg and 100-mg doses was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis, according to the results of the ongoing phase 3 MAESTRO-NASH trial published in The New England Journal of Medicine.

Although certain findings from this trial were initially presented at the European Association for the Study of the Liver Congress 2023, the publication of the full peer-reviewed paper represents a potentially significant milestone in the management of NASH, a disease for which there is currently no approved pharmacologic treatment. 

Harrison_Stephen_A_TEXAS_web.jpg

“Data for the first 1,050 patients from the MAESTRO-NASH trial, together with data from completed resmetirom trials, support the potential for resmetirom to provide benefit to patients with NASH and liver fibrosis,” wrote the authors, led by principal investigator Stephen Harrison, MD, chairman of Pinnacle Clinical Research and Summit Clinical Research in San Antonio, Texas. 

The trial uses the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to metabolic dysfunction–associated steatohepatitis (MASH) and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. 
 

A Closer Look at MAESTRO-NASH

Investigators enrolled 996 participants who were randomly assigned to receive placebo or resmetirom at 80 mg or 100 mg. Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score. 

They observed that patients receiving resmetirom had a significant improvement across both doses and both primary endpoints. 

NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, vs 9.7% on placebo. Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the increasing-dose groups, respectively, compared with 14.2% on placebo (P < .001 for both doses compared with placebo). 

The effects with resmetirom were consistent across key subgroups, regardless of baseline fibrosis stage; baseline NAFLD activity score; or type 2 diabetes status, age, and sex. 

“Multiple non-invasive tests for NASH, steatosis, and fibrosis (including blood biomarkers and imaging) showed a similar direction of effects favoring resmetirom treatment, which supports the findings for the primary end points,” Dr. Harrison and colleagues wrote. 

The majority of patients with NASH also have diabetes. As a result, patients with NASH are known to have a high cardiovascular risk and mortality. However, MAESTRO-NASH investigators reported that compared with those receiving placebo, patients on resmetirom experienced reductions in levels of a broad range of atherogenic lipids and lipoproteins, including low-density lipoprotein (LDL) cholesterol, non–high-density lipoprotein cholesterol, triglycerides, apolipoprotein B, and lipoprotein(a). These findings were consistent with earlier studies of resmetirom. 

From baseline to week 24, LDL cholesterol levels were reduced by -13.6% in the 80-mg and by -16.3% in the 100-mg resmetirom groups compared with 0.1% in the placebo group (P < .001).

More patients in the 100-mg group than in the 80-mg or placebo groups discontinued the trial due to adverse events (6.8% vs 1.8% and 2.2%, respectively). Diarrhea and nausea occurred more frequently in the resmetirom groups than in the placebo group. Serious adverse events occurred with similar incidences across the 100-mg, 80-mg, and placebo groups (12.7%, 10.9%, and 11.5%, respectively).

Although to date the MAESTRO-NASH trial lacks clinical outcomes, over its planned duration of 54 months, investigators will accrue data on liver-related outcomes, including progression to cirrhosis. Likewise, long-term safety data will become available with the trial’s completion. 

Disclosure forms provided by the authors are available with the full text of the NEJM paper at NEJM.org. 

A version of this article appeared on Medscape.com.

The oral thyroid hormone receptor beta-selective agonist resmetirom (Madrigal Pharmaceuticals) in both 80-mg and 100-mg doses was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis, according to the results of the ongoing phase 3 MAESTRO-NASH trial published in The New England Journal of Medicine.

Although certain findings from this trial were initially presented at the European Association for the Study of the Liver Congress 2023, the publication of the full peer-reviewed paper represents a potentially significant milestone in the management of NASH, a disease for which there is currently no approved pharmacologic treatment. 

Harrison_Stephen_A_TEXAS_web.jpg

“Data for the first 1,050 patients from the MAESTRO-NASH trial, together with data from completed resmetirom trials, support the potential for resmetirom to provide benefit to patients with NASH and liver fibrosis,” wrote the authors, led by principal investigator Stephen Harrison, MD, chairman of Pinnacle Clinical Research and Summit Clinical Research in San Antonio, Texas. 

The trial uses the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to metabolic dysfunction–associated steatohepatitis (MASH) and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. 
 

A Closer Look at MAESTRO-NASH

Investigators enrolled 996 participants who were randomly assigned to receive placebo or resmetirom at 80 mg or 100 mg. Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score. 

They observed that patients receiving resmetirom had a significant improvement across both doses and both primary endpoints. 

NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, vs 9.7% on placebo. Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the increasing-dose groups, respectively, compared with 14.2% on placebo (P < .001 for both doses compared with placebo). 

The effects with resmetirom were consistent across key subgroups, regardless of baseline fibrosis stage; baseline NAFLD activity score; or type 2 diabetes status, age, and sex. 

“Multiple non-invasive tests for NASH, steatosis, and fibrosis (including blood biomarkers and imaging) showed a similar direction of effects favoring resmetirom treatment, which supports the findings for the primary end points,” Dr. Harrison and colleagues wrote. 

The majority of patients with NASH also have diabetes. As a result, patients with NASH are known to have a high cardiovascular risk and mortality. However, MAESTRO-NASH investigators reported that compared with those receiving placebo, patients on resmetirom experienced reductions in levels of a broad range of atherogenic lipids and lipoproteins, including low-density lipoprotein (LDL) cholesterol, non–high-density lipoprotein cholesterol, triglycerides, apolipoprotein B, and lipoprotein(a). These findings were consistent with earlier studies of resmetirom. 

From baseline to week 24, LDL cholesterol levels were reduced by -13.6% in the 80-mg and by -16.3% in the 100-mg resmetirom groups compared with 0.1% in the placebo group (P < .001).

More patients in the 100-mg group than in the 80-mg or placebo groups discontinued the trial due to adverse events (6.8% vs 1.8% and 2.2%, respectively). Diarrhea and nausea occurred more frequently in the resmetirom groups than in the placebo group. Serious adverse events occurred with similar incidences across the 100-mg, 80-mg, and placebo groups (12.7%, 10.9%, and 11.5%, respectively).

Although to date the MAESTRO-NASH trial lacks clinical outcomes, over its planned duration of 54 months, investigators will accrue data on liver-related outcomes, including progression to cirrhosis. Likewise, long-term safety data will become available with the trial’s completion. 

Disclosure forms provided by the authors are available with the full text of the NEJM paper at NEJM.org. 

A version of this article appeared on Medscape.com.

GLASGOW – An interactive digital decision tool that individualizes menopause care received praise from primary care clinicians in the United Kingdom, who said it could improve patient care and streamline office visits.

The tool, called Wellspring, helps clarify menopause guidelines from the U.K.’s National Institute for Health and Care Excellence while fostering shared decision-making with evidence-based data.  

“Access to hormone replacement therapy [HRT], as well as decision-making around treatment for menopausal symptoms, is often complicated by concerns around its safety, and there is still a knowledge and a confidence gap among health care professionals causing reluctance to prescribe HRT,”  said Aini Kamal, MSc, from University College London. Ms. Kamal presented results of a survey about the tool at the annual meeting of the Royal College of General Practitioners.

For the study, Ms. Kamal, Daniel Reisel, MBBS, PhD, a gynecologist at UCL, and colleagues evaluated Wellspring with doctors, nurses, and pharmacists.

“Ensuring that women receive education around symptoms, so that they are empowered, is a key part of optimizing their care and sharing decision-making,” Dr. Reisel said in an interview. He added that U.K. primary care had seen an increase in cases of women presenting with symptoms associated with the perimenopause and menopause at a time when U.K. Members of Parliament are debating whether to make it mandatory for all women to have menopause check-up in their early 40s.

The online survey was completed by 280 participants, and respondents were primarily GPs with several years of relevant prescribing practice. Of those, 93% found information from national guidelines to be accurately presented in the tool, and 97% said they would recommend this decision aid to other health care professionals, Ms. Kamal reported.

Nearly all participants said they could see themselves using the tool with patients in the clinic or as an adjunct to virtual sessions. “This [finding] was particularly important because it demonstrates the clinical potential this tool has,” she said.

 

One consult, too many problems

Louise Newson, MBChB, who runs the U.K.’s largest menopause clinic, said primary care appointments are often time-pressured and follow a “’one problem-one consultation’” policy. As such, women are often thinking ‘Do I go with my joint pains, or my palpitations, tinnitus, or what?’ If a patient presents with tinnitus, a doctor might focus on the potential of an inner ear problem rather than a hormone deficiency, but I do know that if the woman is perimenopausal or menopausal, we often look to replace the missing hormones, and then if the tinnitus doesn’t improve we can revisit the ear problem.” 

Dr. Newson noted that 17% of women in her clinics have had more than six GP visits in the year before she sees them, but in the year following, this figure drops to 1%. Acknowledging that a menopause consultation for a GP is time-consuming, Dr. Newson pointed out that taking time initially with the patient “means it will reduce the number of future consultations quickly, but more importantly, we also know that taking HRT reduces long-term risk of serious diseases, including heart disease and osteoporosis.”

The digital tool can be used by both doctors and patients to help women work through their symptoms and equip them with knowledge so their GP visits are more productive.

“When we see women who are empowered with knowledge [about menopause symptoms], then the consultations are quicker and essentially place the patient central to the discussion,” Dr. Newson said.

Ed Russell-Smith, MBChB, a GP in Scotland who moderated the session, said the tool “lays out a nicely structured approach and provides modern treatment options and resources for patients.”

However, he added “we also need to remember there are potential harms to be done from HRT too. It’s vitally important that while patients might see HRT as a panacea, doctors need to balance this with the risks involved for each individual. As a tool, I think Wellspring can help us in this respect to apply general principles to that patient and individualize treatment.”

Dr. Reisel, Dr. Newson, Ms. Kamal, and Dr. Russell-Smith disclosed no relevant financial relationships. The Wellspring Decision Aid was supported by UCL’s Institute for Women’s Health. The Newson Health clinic is fully private, but research is done via the nonprofit arm, which is supported by the clinic. There is no pharma involvement.

A version of this article first appeared on Medscape.com.

GLASGOW – An interactive digital decision tool that individualizes menopause care received praise from primary care clinicians in the United Kingdom, who said it could improve patient care and streamline office visits.

The tool, called Wellspring, helps clarify menopause guidelines from the U.K.’s National Institute for Health and Care Excellence while fostering shared decision-making with evidence-based data.  

“Access to hormone replacement therapy [HRT], as well as decision-making around treatment for menopausal symptoms, is often complicated by concerns around its safety, and there is still a knowledge and a confidence gap among health care professionals causing reluctance to prescribe HRT,”  said Aini Kamal, MSc, from University College London. Ms. Kamal presented results of a survey about the tool at the annual meeting of the Royal College of General Practitioners.

For the study, Ms. Kamal, Daniel Reisel, MBBS, PhD, a gynecologist at UCL, and colleagues evaluated Wellspring with doctors, nurses, and pharmacists.

“Ensuring that women receive education around symptoms, so that they are empowered, is a key part of optimizing their care and sharing decision-making,” Dr. Reisel said in an interview. He added that U.K. primary care had seen an increase in cases of women presenting with symptoms associated with the perimenopause and menopause at a time when U.K. Members of Parliament are debating whether to make it mandatory for all women to have menopause check-up in their early 40s.

The online survey was completed by 280 participants, and respondents were primarily GPs with several years of relevant prescribing practice. Of those, 93% found information from national guidelines to be accurately presented in the tool, and 97% said they would recommend this decision aid to other health care professionals, Ms. Kamal reported.

Nearly all participants said they could see themselves using the tool with patients in the clinic or as an adjunct to virtual sessions. “This [finding] was particularly important because it demonstrates the clinical potential this tool has,” she said.

 

One consult, too many problems

Louise Newson, MBChB, who runs the U.K.’s largest menopause clinic, said primary care appointments are often time-pressured and follow a “’one problem-one consultation’” policy. As such, women are often thinking ‘Do I go with my joint pains, or my palpitations, tinnitus, or what?’ If a patient presents with tinnitus, a doctor might focus on the potential of an inner ear problem rather than a hormone deficiency, but I do know that if the woman is perimenopausal or menopausal, we often look to replace the missing hormones, and then if the tinnitus doesn’t improve we can revisit the ear problem.” 

Dr. Newson noted that 17% of women in her clinics have had more than six GP visits in the year before she sees them, but in the year following, this figure drops to 1%. Acknowledging that a menopause consultation for a GP is time-consuming, Dr. Newson pointed out that taking time initially with the patient “means it will reduce the number of future consultations quickly, but more importantly, we also know that taking HRT reduces long-term risk of serious diseases, including heart disease and osteoporosis.”

The digital tool can be used by both doctors and patients to help women work through their symptoms and equip them with knowledge so their GP visits are more productive.

“When we see women who are empowered with knowledge [about menopause symptoms], then the consultations are quicker and essentially place the patient central to the discussion,” Dr. Newson said.

Ed Russell-Smith, MBChB, a GP in Scotland who moderated the session, said the tool “lays out a nicely structured approach and provides modern treatment options and resources for patients.”

However, he added “we also need to remember there are potential harms to be done from HRT too. It’s vitally important that while patients might see HRT as a panacea, doctors need to balance this with the risks involved for each individual. As a tool, I think Wellspring can help us in this respect to apply general principles to that patient and individualize treatment.”

Dr. Reisel, Dr. Newson, Ms. Kamal, and Dr. Russell-Smith disclosed no relevant financial relationships. The Wellspring Decision Aid was supported by UCL’s Institute for Women’s Health. The Newson Health clinic is fully private, but research is done via the nonprofit arm, which is supported by the clinic. There is no pharma involvement.

A version of this article first appeared on Medscape.com.

GLASGOW – An interactive digital decision tool that individualizes menopause care received praise from primary care clinicians in the United Kingdom, who said it could improve patient care and streamline office visits.

The tool, called Wellspring, helps clarify menopause guidelines from the U.K.’s National Institute for Health and Care Excellence while fostering shared decision-making with evidence-based data.  

“Access to hormone replacement therapy [HRT], as well as decision-making around treatment for menopausal symptoms, is often complicated by concerns around its safety, and there is still a knowledge and a confidence gap among health care professionals causing reluctance to prescribe HRT,”  said Aini Kamal, MSc, from University College London. Ms. Kamal presented results of a survey about the tool at the annual meeting of the Royal College of General Practitioners.

For the study, Ms. Kamal, Daniel Reisel, MBBS, PhD, a gynecologist at UCL, and colleagues evaluated Wellspring with doctors, nurses, and pharmacists.

“Ensuring that women receive education around symptoms, so that they are empowered, is a key part of optimizing their care and sharing decision-making,” Dr. Reisel said in an interview. He added that U.K. primary care had seen an increase in cases of women presenting with symptoms associated with the perimenopause and menopause at a time when U.K. Members of Parliament are debating whether to make it mandatory for all women to have menopause check-up in their early 40s.

The online survey was completed by 280 participants, and respondents were primarily GPs with several years of relevant prescribing practice. Of those, 93% found information from national guidelines to be accurately presented in the tool, and 97% said they would recommend this decision aid to other health care professionals, Ms. Kamal reported.

Nearly all participants said they could see themselves using the tool with patients in the clinic or as an adjunct to virtual sessions. “This [finding] was particularly important because it demonstrates the clinical potential this tool has,” she said.

 

One consult, too many problems

Louise Newson, MBChB, who runs the U.K.’s largest menopause clinic, said primary care appointments are often time-pressured and follow a “’one problem-one consultation’” policy. As such, women are often thinking ‘Do I go with my joint pains, or my palpitations, tinnitus, or what?’ If a patient presents with tinnitus, a doctor might focus on the potential of an inner ear problem rather than a hormone deficiency, but I do know that if the woman is perimenopausal or menopausal, we often look to replace the missing hormones, and then if the tinnitus doesn’t improve we can revisit the ear problem.” 

Dr. Newson noted that 17% of women in her clinics have had more than six GP visits in the year before she sees them, but in the year following, this figure drops to 1%. Acknowledging that a menopause consultation for a GP is time-consuming, Dr. Newson pointed out that taking time initially with the patient “means it will reduce the number of future consultations quickly, but more importantly, we also know that taking HRT reduces long-term risk of serious diseases, including heart disease and osteoporosis.”

The digital tool can be used by both doctors and patients to help women work through their symptoms and equip them with knowledge so their GP visits are more productive.

“When we see women who are empowered with knowledge [about menopause symptoms], then the consultations are quicker and essentially place the patient central to the discussion,” Dr. Newson said.

Ed Russell-Smith, MBChB, a GP in Scotland who moderated the session, said the tool “lays out a nicely structured approach and provides modern treatment options and resources for patients.”

However, he added “we also need to remember there are potential harms to be done from HRT too. It’s vitally important that while patients might see HRT as a panacea, doctors need to balance this with the risks involved for each individual. As a tool, I think Wellspring can help us in this respect to apply general principles to that patient and individualize treatment.”

Dr. Reisel, Dr. Newson, Ms. Kamal, and Dr. Russell-Smith disclosed no relevant financial relationships. The Wellspring Decision Aid was supported by UCL’s Institute for Women’s Health. The Newson Health clinic is fully private, but research is done via the nonprofit arm, which is supported by the clinic. There is no pharma involvement.

A version of this article first appeared on Medscape.com.

COPENHAGEN – People with precancerous colonic lesions show significant differences in their gut microbiome, compared with the general population up to 5 years before the lesions develop, according to a large, 22-year analysis from the Dutch Microbiome Project cohort study.

The findings suggest a possible role for gut microbiota in the development of colorectal lesions and cancer, said study lead Ranko Gacesa, PhD, from the department of gastroenterology, University of Groningen (the Netherlands), who presented the results at the annual United European Gastroenterology Week.

“It [also] suggests that gut bacteria might enhance currently used noninvasive fecal tests for the detection of colorectal polyps, and even that microbiome-modulating therapies might play a role in prevention of colorectal cancer,” said Dr. Gacesa, who won the award for best abstract in the meeting session.

The gut microbiome is known to be linked to colorectal cancer (CRC); in particular, the bacteria Bacteroides fragilis and Alistipes finegoldii have been found to cause CRC in mouse models, explained Dr. Gacesa.

In the current study, Dr. Gacesa and colleagues looked at the potential for the gut microbiome in humans to play a role in the detection of precancerous colonic lesions. The noninvasive fecal immunochemical test (FIT), recently shown to be a preference among patients, produces a high number of false-positive results, leading to many unnecessary colonoscopies.

“It has been calculated that the use of a fecal microbiota analysis combined with FIT in the early-stage prediction of CRC could result in a high true-positive rate and a low false-positive rate,” said Dr. Gacesa. “In this way, we might reduce the false-positive rate by around 50%. 

“Ideally, we don’t want to detect cancer when it is already established and is hard to treat. We want to detect it as early in its development as possible,” he said.
 

Longitudinal analysis using large Dutch databases

To determine the direction of the relationship between CRC and the gut microbiome, the Dutch researchers conducted a longitudinal analysis from 2000 to 2022, looking at whether CRC alters the gut microbiome, as well as whether changes in the microbiome contribute to the development of precancerous lesions and CRC.

They drew on data from the Dutch colorectal cancer screening program, comprising FIT results in people aged 55 years and older, and colonoscopy if referred. They recorded cases of colonic biopsies from the extensive Dutch national database of medical biopsies. These were then linked with Dutch microbiome project data sourced from fecal samples of 8208 individuals taken between 2012 and 2015.

“This allowed us to associate gut microbiome compositions and functions to detailed histological information about precancerous lesions and CRC, including when lesions were detected relative to fecal sampling [and a reading of the gut microbiome],” Dr. Gacesa explained. 

The analysis determined the composition, function, and genomic profiles of gut microbiota in participants who developed precancerous colorectal lesions before fecal sampling from 2000 to 2015, and in those participants who developed lesions after fecal sampling, between 2015 and 2022. Clinical phenotypes, comprising the type and size of lesions, were noted. The control group included 2123 individuals from the general population with normal colonoscopy findings.
 

More precancerous lesions found after fecal sampling

There were more cases of precancerous lesions found after fecal sampling, reported Dr. Gacesa.

Before fecal sampling, 219 participants had colonic lesions, including low-grade dysplasia, high-grade dysplasia, and serrated polyps, and 26 cases of CRC. A total of 315 participants developed assorted colonic lesions after fecal sampling, with a total of 29 cases of CRC.

When the researchers looked at microbiome diversity in people who had experienced precancerous colonic lesions 1-5 years before fecal sampling, they found that diversity was lower, compared with controls. Microbiome diversity was also decreased in participants who developed colonic lesions after sampling.

The microbiome composition and function were different between patients with preexisting and future lesions, and varied based on the types of lesion.

“We saw a drop in some commensal bacteria, including Faecalibacterium, in both those with recent pathologies and those who developed them in the future. We also saw a massive spike in Alistipes finegoldii in those who had CRC, strongly suggesting it is closely linked to CRC in people,” reported Dr. Gacesa.

Among bacterial species linked with the future development of precancerous lesions were those from the family of Lachnospiraceae, and the genera Roseburia and Eubacterium. Microbiome composition had a moderate predictive power for future lesions and CRC.

“Precancerous lesions are linked to the gut microbiome,” Dr. Gacesa said. “Adenomas – both preexisting ones (before fecal sampling), and ones that came after fecal sampling – are significantly linked to the microbiome composition.”
 

More time needed

Loris Lopetuso, MD, gastroenterologist, from Fondazione Policlinico Universitario Agostino Gemelli, Rome, who comoderated the session, remarked that the data were intriguing and important.

“We really need to find new predictors of tumorigenesis,” he said. “We already have some good predictors, mainly FIT, but these are not enough. These gut microbiota look promising.”

He added that the study by Dr. Gacesa’s team was one of the largest he had seen. “But I would note that, methodologically, we need to remember that the time between a fecal sample and the development of polyps can be very large,” Dr. Lopetuso emphasized. “This study looked at around 5 years only. Also, the microbiota can change from one day to the other in response to stress, diet, and many other things.” 

However, “this could be the beginning of a longitudinal study between cases and controls because many years are needed,” he added.

Dr. Gacesa has received funding from Janssen Pharmaceuticals for an unrelated research project. He is a paid R&D consultant for Esox Biologics Ltd for topics unrelated to this project. Dr. Lopetuso reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

COPENHAGEN – People with precancerous colonic lesions show significant differences in their gut microbiome, compared with the general population up to 5 years before the lesions develop, according to a large, 22-year analysis from the Dutch Microbiome Project cohort study.

The findings suggest a possible role for gut microbiota in the development of colorectal lesions and cancer, said study lead Ranko Gacesa, PhD, from the department of gastroenterology, University of Groningen (the Netherlands), who presented the results at the annual United European Gastroenterology Week.

“It [also] suggests that gut bacteria might enhance currently used noninvasive fecal tests for the detection of colorectal polyps, and even that microbiome-modulating therapies might play a role in prevention of colorectal cancer,” said Dr. Gacesa, who won the award for best abstract in the meeting session.

The gut microbiome is known to be linked to colorectal cancer (CRC); in particular, the bacteria Bacteroides fragilis and Alistipes finegoldii have been found to cause CRC in mouse models, explained Dr. Gacesa.

In the current study, Dr. Gacesa and colleagues looked at the potential for the gut microbiome in humans to play a role in the detection of precancerous colonic lesions. The noninvasive fecal immunochemical test (FIT), recently shown to be a preference among patients, produces a high number of false-positive results, leading to many unnecessary colonoscopies.

“It has been calculated that the use of a fecal microbiota analysis combined with FIT in the early-stage prediction of CRC could result in a high true-positive rate and a low false-positive rate,” said Dr. Gacesa. “In this way, we might reduce the false-positive rate by around 50%. 

“Ideally, we don’t want to detect cancer when it is already established and is hard to treat. We want to detect it as early in its development as possible,” he said.
 

Longitudinal analysis using large Dutch databases

To determine the direction of the relationship between CRC and the gut microbiome, the Dutch researchers conducted a longitudinal analysis from 2000 to 2022, looking at whether CRC alters the gut microbiome, as well as whether changes in the microbiome contribute to the development of precancerous lesions and CRC.

They drew on data from the Dutch colorectal cancer screening program, comprising FIT results in people aged 55 years and older, and colonoscopy if referred. They recorded cases of colonic biopsies from the extensive Dutch national database of medical biopsies. These were then linked with Dutch microbiome project data sourced from fecal samples of 8208 individuals taken between 2012 and 2015.

“This allowed us to associate gut microbiome compositions and functions to detailed histological information about precancerous lesions and CRC, including when lesions were detected relative to fecal sampling [and a reading of the gut microbiome],” Dr. Gacesa explained. 

The analysis determined the composition, function, and genomic profiles of gut microbiota in participants who developed precancerous colorectal lesions before fecal sampling from 2000 to 2015, and in those participants who developed lesions after fecal sampling, between 2015 and 2022. Clinical phenotypes, comprising the type and size of lesions, were noted. The control group included 2123 individuals from the general population with normal colonoscopy findings.
 

More precancerous lesions found after fecal sampling

There were more cases of precancerous lesions found after fecal sampling, reported Dr. Gacesa.

Before fecal sampling, 219 participants had colonic lesions, including low-grade dysplasia, high-grade dysplasia, and serrated polyps, and 26 cases of CRC. A total of 315 participants developed assorted colonic lesions after fecal sampling, with a total of 29 cases of CRC.

When the researchers looked at microbiome diversity in people who had experienced precancerous colonic lesions 1-5 years before fecal sampling, they found that diversity was lower, compared with controls. Microbiome diversity was also decreased in participants who developed colonic lesions after sampling.

The microbiome composition and function were different between patients with preexisting and future lesions, and varied based on the types of lesion.

“We saw a drop in some commensal bacteria, including Faecalibacterium, in both those with recent pathologies and those who developed them in the future. We also saw a massive spike in Alistipes finegoldii in those who had CRC, strongly suggesting it is closely linked to CRC in people,” reported Dr. Gacesa.

Among bacterial species linked with the future development of precancerous lesions were those from the family of Lachnospiraceae, and the genera Roseburia and Eubacterium. Microbiome composition had a moderate predictive power for future lesions and CRC.

“Precancerous lesions are linked to the gut microbiome,” Dr. Gacesa said. “Adenomas – both preexisting ones (before fecal sampling), and ones that came after fecal sampling – are significantly linked to the microbiome composition.”
 

More time needed

Loris Lopetuso, MD, gastroenterologist, from Fondazione Policlinico Universitario Agostino Gemelli, Rome, who comoderated the session, remarked that the data were intriguing and important.

“We really need to find new predictors of tumorigenesis,” he said. “We already have some good predictors, mainly FIT, but these are not enough. These gut microbiota look promising.”

He added that the study by Dr. Gacesa’s team was one of the largest he had seen. “But I would note that, methodologically, we need to remember that the time between a fecal sample and the development of polyps can be very large,” Dr. Lopetuso emphasized. “This study looked at around 5 years only. Also, the microbiota can change from one day to the other in response to stress, diet, and many other things.” 

However, “this could be the beginning of a longitudinal study between cases and controls because many years are needed,” he added.

Dr. Gacesa has received funding from Janssen Pharmaceuticals for an unrelated research project. He is a paid R&D consultant for Esox Biologics Ltd for topics unrelated to this project. Dr. Lopetuso reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

COPENHAGEN – People with precancerous colonic lesions show significant differences in their gut microbiome, compared with the general population up to 5 years before the lesions develop, according to a large, 22-year analysis from the Dutch Microbiome Project cohort study.

The findings suggest a possible role for gut microbiota in the development of colorectal lesions and cancer, said study lead Ranko Gacesa, PhD, from the department of gastroenterology, University of Groningen (the Netherlands), who presented the results at the annual United European Gastroenterology Week.

“It [also] suggests that gut bacteria might enhance currently used noninvasive fecal tests for the detection of colorectal polyps, and even that microbiome-modulating therapies might play a role in prevention of colorectal cancer,” said Dr. Gacesa, who won the award for best abstract in the meeting session.

The gut microbiome is known to be linked to colorectal cancer (CRC); in particular, the bacteria Bacteroides fragilis and Alistipes finegoldii have been found to cause CRC in mouse models, explained Dr. Gacesa.

In the current study, Dr. Gacesa and colleagues looked at the potential for the gut microbiome in humans to play a role in the detection of precancerous colonic lesions. The noninvasive fecal immunochemical test (FIT), recently shown to be a preference among patients, produces a high number of false-positive results, leading to many unnecessary colonoscopies.

“It has been calculated that the use of a fecal microbiota analysis combined with FIT in the early-stage prediction of CRC could result in a high true-positive rate and a low false-positive rate,” said Dr. Gacesa. “In this way, we might reduce the false-positive rate by around 50%. 

“Ideally, we don’t want to detect cancer when it is already established and is hard to treat. We want to detect it as early in its development as possible,” he said.
 

Longitudinal analysis using large Dutch databases

To determine the direction of the relationship between CRC and the gut microbiome, the Dutch researchers conducted a longitudinal analysis from 2000 to 2022, looking at whether CRC alters the gut microbiome, as well as whether changes in the microbiome contribute to the development of precancerous lesions and CRC.

They drew on data from the Dutch colorectal cancer screening program, comprising FIT results in people aged 55 years and older, and colonoscopy if referred. They recorded cases of colonic biopsies from the extensive Dutch national database of medical biopsies. These were then linked with Dutch microbiome project data sourced from fecal samples of 8208 individuals taken between 2012 and 2015.

“This allowed us to associate gut microbiome compositions and functions to detailed histological information about precancerous lesions and CRC, including when lesions were detected relative to fecal sampling [and a reading of the gut microbiome],” Dr. Gacesa explained. 

The analysis determined the composition, function, and genomic profiles of gut microbiota in participants who developed precancerous colorectal lesions before fecal sampling from 2000 to 2015, and in those participants who developed lesions after fecal sampling, between 2015 and 2022. Clinical phenotypes, comprising the type and size of lesions, were noted. The control group included 2123 individuals from the general population with normal colonoscopy findings.
 

More precancerous lesions found after fecal sampling

There were more cases of precancerous lesions found after fecal sampling, reported Dr. Gacesa.

Before fecal sampling, 219 participants had colonic lesions, including low-grade dysplasia, high-grade dysplasia, and serrated polyps, and 26 cases of CRC. A total of 315 participants developed assorted colonic lesions after fecal sampling, with a total of 29 cases of CRC.

When the researchers looked at microbiome diversity in people who had experienced precancerous colonic lesions 1-5 years before fecal sampling, they found that diversity was lower, compared with controls. Microbiome diversity was also decreased in participants who developed colonic lesions after sampling.

The microbiome composition and function were different between patients with preexisting and future lesions, and varied based on the types of lesion.

“We saw a drop in some commensal bacteria, including Faecalibacterium, in both those with recent pathologies and those who developed them in the future. We also saw a massive spike in Alistipes finegoldii in those who had CRC, strongly suggesting it is closely linked to CRC in people,” reported Dr. Gacesa.

Among bacterial species linked with the future development of precancerous lesions were those from the family of Lachnospiraceae, and the genera Roseburia and Eubacterium. Microbiome composition had a moderate predictive power for future lesions and CRC.

“Precancerous lesions are linked to the gut microbiome,” Dr. Gacesa said. “Adenomas – both preexisting ones (before fecal sampling), and ones that came after fecal sampling – are significantly linked to the microbiome composition.”
 

More time needed

Loris Lopetuso, MD, gastroenterologist, from Fondazione Policlinico Universitario Agostino Gemelli, Rome, who comoderated the session, remarked that the data were intriguing and important.

“We really need to find new predictors of tumorigenesis,” he said. “We already have some good predictors, mainly FIT, but these are not enough. These gut microbiota look promising.”

He added that the study by Dr. Gacesa’s team was one of the largest he had seen. “But I would note that, methodologically, we need to remember that the time between a fecal sample and the development of polyps can be very large,” Dr. Lopetuso emphasized. “This study looked at around 5 years only. Also, the microbiota can change from one day to the other in response to stress, diet, and many other things.” 

However, “this could be the beginning of a longitudinal study between cases and controls because many years are needed,” he added.

Dr. Gacesa has received funding from Janssen Pharmaceuticals for an unrelated research project. He is a paid R&D consultant for Esox Biologics Ltd for topics unrelated to this project. Dr. Lopetuso reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

GLASGOW – Three-quarters of women going through perimenopause and menopause experience unexpected distressing, debilitating, and embarrassing symptoms but often fail to receive appropriate treatment, a large U.K.-based survey found. 

“For too long, many people have thought of menopause as just hot flashes and vaginal dryness. But we know hormones work all over our body, so there are many symptoms beyond that,” said Daniel Reisel, MBBS, PhD, a gynecologist at University College London, who presented the survey findings at the 2023 annual meeting of the Royal College of General Practitioners.

Primary care physicians in the United Kingdom have seen an increase in cases of women presenting with symptoms associated with menopause at a time when the country’s Parliament is debating whether all women should have a menopause check-up in their early 40s, he said.  

Still, only around 14% of menopausal women in the United Kingdom are prescribed hormone replacement therapy (HRT), despite national and international guidelines clearly stating the benefits of the treatment generally outweigh the risks.

Louise Newson, MBChB, who runs the U.K.’s largest menopause clinic, said many women with symptoms of menopause feel the medical system “gaslights” them – dismissing their concerns as trivial or even fabricated.

In her clinic, she typically sees many women with poor sleep, as well as muscle and joint pains. “Yet [when they visit their GPs], they are incorrectly told that it can’t be hormones because they’re still having periods,” she said.
 

Prescribed antidepressants often precede HRT

The new study sought to learn what women knew and experienced with respect to menopause symptoms and what they thought was important.

Of the 5,744 women who responded to the survey, 79.4% were aged 40-60 years and 84.6% were White. “The survey respondents were not different from the distribution of ethnicities we see in NHS menopause care,” said Dr. Reisel, adding that “the barriers are greater for women in poorer areas and for those who are non-White.”

A total of 30.4% had two to five hospital consultations before the health care professional considered that symptoms were related to changing hormone levels; 38.5% were offered antidepressants before HRT. Nearly all (94.6%) said they had experienced negative mood changes and emotions since becoming perimenopausal or menopausal; of these, 19.1% were formally diagnosed with depression or a mood disorder.

“This all just highlights the frustrations I feel around menopause care,” Dr. Newson said. “Women are often not given the tools to properly understand what’s going on and then they don’t ask for the right treatment, and many are given antidepressants. It’s still medicalizing the menopause but in a different way.”
 

Education gap

The researchers also asked women if they had experienced any surprising or unexpected symptoms since becoming perimenopausal or menopausal. To this question, 74.2% said they had. Joint pain was the most common unexpected issue (34%), followed by dry eyes (26%), heart palpitations (25%), and hair issues such as dryness, thinning, and loss (20%).

Dr. Reisel said words used to describe these symptoms in free text responses included “distressing,” “debilitating,” “depressing,” and “embarrassing.”

“When an early-50s woman comes to the GP with dry eyes, joint pain, or recurrent urinary tract infections, for example, before prescribing ibuprofen, or antibiotics, GPs should consider replacing a woman’s hormones and then see what is left in terms of symptoms,” he said.

Cognitive problems and negative mood changes also are common and often overlooked, Dr. Reisel noted. “We often see striking improvements in mood and cognition in women who are prescribed testosterone for low libido, yet symptoms in these areas are not currently an indication to start treatment,” he said. “Data from Newson Health show that 18% have suicidal thoughts in the past 2 weeks, and not many people think about this.”

Much of this lack of understanding around unexpected symptoms relates to a lack of awareness and education. “It goes back to primary and secondary school, and more broadly, these issues are not often talked about in society,” he said.  

Dr. Reisel also noted that language and cultural barriers often stand in the way. “Many cultures don’t discuss menopause and hormone health in general at all. For example, in Bengali, spoken by 300 million people, there is no word in for menopause. So many women are gaslighted when they try and describe their symptoms, or they’re simply just unaware.”

Dr. Reisel and Dr. Newson reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

GLASGOW – Three-quarters of women going through perimenopause and menopause experience unexpected distressing, debilitating, and embarrassing symptoms but often fail to receive appropriate treatment, a large U.K.-based survey found. 

“For too long, many people have thought of menopause as just hot flashes and vaginal dryness. But we know hormones work all over our body, so there are many symptoms beyond that,” said Daniel Reisel, MBBS, PhD, a gynecologist at University College London, who presented the survey findings at the 2023 annual meeting of the Royal College of General Practitioners.

Primary care physicians in the United Kingdom have seen an increase in cases of women presenting with symptoms associated with menopause at a time when the country’s Parliament is debating whether all women should have a menopause check-up in their early 40s, he said.  

Still, only around 14% of menopausal women in the United Kingdom are prescribed hormone replacement therapy (HRT), despite national and international guidelines clearly stating the benefits of the treatment generally outweigh the risks.

Louise Newson, MBChB, who runs the U.K.’s largest menopause clinic, said many women with symptoms of menopause feel the medical system “gaslights” them – dismissing their concerns as trivial or even fabricated.

In her clinic, she typically sees many women with poor sleep, as well as muscle and joint pains. “Yet [when they visit their GPs], they are incorrectly told that it can’t be hormones because they’re still having periods,” she said.
 

Prescribed antidepressants often precede HRT

The new study sought to learn what women knew and experienced with respect to menopause symptoms and what they thought was important.

Of the 5,744 women who responded to the survey, 79.4% were aged 40-60 years and 84.6% were White. “The survey respondents were not different from the distribution of ethnicities we see in NHS menopause care,” said Dr. Reisel, adding that “the barriers are greater for women in poorer areas and for those who are non-White.”

A total of 30.4% had two to five hospital consultations before the health care professional considered that symptoms were related to changing hormone levels; 38.5% were offered antidepressants before HRT. Nearly all (94.6%) said they had experienced negative mood changes and emotions since becoming perimenopausal or menopausal; of these, 19.1% were formally diagnosed with depression or a mood disorder.

“This all just highlights the frustrations I feel around menopause care,” Dr. Newson said. “Women are often not given the tools to properly understand what’s going on and then they don’t ask for the right treatment, and many are given antidepressants. It’s still medicalizing the menopause but in a different way.”
 

Education gap

The researchers also asked women if they had experienced any surprising or unexpected symptoms since becoming perimenopausal or menopausal. To this question, 74.2% said they had. Joint pain was the most common unexpected issue (34%), followed by dry eyes (26%), heart palpitations (25%), and hair issues such as dryness, thinning, and loss (20%).

Dr. Reisel said words used to describe these symptoms in free text responses included “distressing,” “debilitating,” “depressing,” and “embarrassing.”

“When an early-50s woman comes to the GP with dry eyes, joint pain, or recurrent urinary tract infections, for example, before prescribing ibuprofen, or antibiotics, GPs should consider replacing a woman’s hormones and then see what is left in terms of symptoms,” he said.

Cognitive problems and negative mood changes also are common and often overlooked, Dr. Reisel noted. “We often see striking improvements in mood and cognition in women who are prescribed testosterone for low libido, yet symptoms in these areas are not currently an indication to start treatment,” he said. “Data from Newson Health show that 18% have suicidal thoughts in the past 2 weeks, and not many people think about this.”

Much of this lack of understanding around unexpected symptoms relates to a lack of awareness and education. “It goes back to primary and secondary school, and more broadly, these issues are not often talked about in society,” he said.  

Dr. Reisel also noted that language and cultural barriers often stand in the way. “Many cultures don’t discuss menopause and hormone health in general at all. For example, in Bengali, spoken by 300 million people, there is no word in for menopause. So many women are gaslighted when they try and describe their symptoms, or they’re simply just unaware.”

Dr. Reisel and Dr. Newson reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

GLASGOW – Three-quarters of women going through perimenopause and menopause experience unexpected distressing, debilitating, and embarrassing symptoms but often fail to receive appropriate treatment, a large U.K.-based survey found. 

“For too long, many people have thought of menopause as just hot flashes and vaginal dryness. But we know hormones work all over our body, so there are many symptoms beyond that,” said Daniel Reisel, MBBS, PhD, a gynecologist at University College London, who presented the survey findings at the 2023 annual meeting of the Royal College of General Practitioners.

Primary care physicians in the United Kingdom have seen an increase in cases of women presenting with symptoms associated with menopause at a time when the country’s Parliament is debating whether all women should have a menopause check-up in their early 40s, he said.  

Still, only around 14% of menopausal women in the United Kingdom are prescribed hormone replacement therapy (HRT), despite national and international guidelines clearly stating the benefits of the treatment generally outweigh the risks.

Louise Newson, MBChB, who runs the U.K.’s largest menopause clinic, said many women with symptoms of menopause feel the medical system “gaslights” them – dismissing their concerns as trivial or even fabricated.

In her clinic, she typically sees many women with poor sleep, as well as muscle and joint pains. “Yet [when they visit their GPs], they are incorrectly told that it can’t be hormones because they’re still having periods,” she said.
 

Prescribed antidepressants often precede HRT

The new study sought to learn what women knew and experienced with respect to menopause symptoms and what they thought was important.

Of the 5,744 women who responded to the survey, 79.4% were aged 40-60 years and 84.6% were White. “The survey respondents were not different from the distribution of ethnicities we see in NHS menopause care,” said Dr. Reisel, adding that “the barriers are greater for women in poorer areas and for those who are non-White.”

A total of 30.4% had two to five hospital consultations before the health care professional considered that symptoms were related to changing hormone levels; 38.5% were offered antidepressants before HRT. Nearly all (94.6%) said they had experienced negative mood changes and emotions since becoming perimenopausal or menopausal; of these, 19.1% were formally diagnosed with depression or a mood disorder.

“This all just highlights the frustrations I feel around menopause care,” Dr. Newson said. “Women are often not given the tools to properly understand what’s going on and then they don’t ask for the right treatment, and many are given antidepressants. It’s still medicalizing the menopause but in a different way.”
 

Education gap

The researchers also asked women if they had experienced any surprising or unexpected symptoms since becoming perimenopausal or menopausal. To this question, 74.2% said they had. Joint pain was the most common unexpected issue (34%), followed by dry eyes (26%), heart palpitations (25%), and hair issues such as dryness, thinning, and loss (20%).

Dr. Reisel said words used to describe these symptoms in free text responses included “distressing,” “debilitating,” “depressing,” and “embarrassing.”

“When an early-50s woman comes to the GP with dry eyes, joint pain, or recurrent urinary tract infections, for example, before prescribing ibuprofen, or antibiotics, GPs should consider replacing a woman’s hormones and then see what is left in terms of symptoms,” he said.

Cognitive problems and negative mood changes also are common and often overlooked, Dr. Reisel noted. “We often see striking improvements in mood and cognition in women who are prescribed testosterone for low libido, yet symptoms in these areas are not currently an indication to start treatment,” he said. “Data from Newson Health show that 18% have suicidal thoughts in the past 2 weeks, and not many people think about this.”

Much of this lack of understanding around unexpected symptoms relates to a lack of awareness and education. “It goes back to primary and secondary school, and more broadly, these issues are not often talked about in society,” he said.  

Dr. Reisel also noted that language and cultural barriers often stand in the way. “Many cultures don’t discuss menopause and hormone health in general at all. For example, in Bengali, spoken by 300 million people, there is no word in for menopause. So many women are gaslighted when they try and describe their symptoms, or they’re simply just unaware.”

Dr. Reisel and Dr. Newson reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.